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September 15, 2020
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https://www.sciencedaily.com/releases/2020/09/200915090129.htm
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Small 'Cain-and-Abel' molecule discovered
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A new bacterial molecule with the unsavory tendency to track down and kill others of its own kind has been discovered in the human microbiome by researchers at Princeton's Department of Chemistry. Named Streptosactin, it is the first small molecule found to exhibit fratricidal activity.
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The discovery by the Seyedsayamdost lab is detailed in the The research describes a veritable needle-in-a-haystack hunt in which streptosactin was located "at the edge of detection." Its production is so minimal and so difficult to track that researchers achieved the results only through a complex interplay of factors.They used a clever bioinformatic search strategy developed a few years ago by Leah Bushin, a sixth-year graduate student in the Seyedsayamdost lab. This "genome-first" approach allowed them to screen molecules for two key characteristics: community behavior (thus uncovering the fratricide), and structural or topological novelty.The researchers then used advanced mass spectrometry tactics to separate out the "signal from noise," manipulating and concentrating the culture extracts over a thousand-fold before locating the sought-after compound after months of searching.The Cain-and-Abel behavior has been found in another bacterium where enzymes or large proteins provide the fratricidal activity -- but never before in a small molecule. The purpose of the behavior is not fully understood. Researchers believe fratricide could contribute to evolutionary fitness by enhancing the genetic makeup of the sibling population."It's crazy, and I was surprised by it, too. This bioactivity is something we would never have predicted," said Mohammad Seyedsayamdost, associate professor of chemistry and associated faculty in molecular biology. "But that's how microbes live -- there is no morality. It's just raw survival."Fratricide is good for the fitness or strength of this species," he added. "It's one way in which this bacterium generates a diverse genetic makeup, so it can increase the chances of surviving any challenge or condition it encounters."The lab's research opens a new window onto the vast, largely unexplored microbiome, that aggregate of microorganisms that lives in the mammalian body and likely plays a significant role in the health of all mammals. So uncharted is the microbiome that it has been described as a frontier every bit as exotic as the surface of the moon or the bottom of the ocean.Natural products chemists like those in the Princeton lab try to discover and understand the molecules that microbes use to interact with their environments. Those interactions allow them to work together, to acquire food material, to compete, even to kill each other. Scientists then use this information to generate drug leads for antibiotics and antivirals; in fact, some 70% of all antibiotics we use clinically come from these sources."Natural product research can be really frustrating because luck plays a significant role. In a way it's a little like fishing," said Bushin, the lead author on the paper Discovery and Biosynthesis of Streptosactin, a Sactipeptide with an Alternative Topology Encoded by Commensal Bacteria in the Human Microbiome, which appears in JACS this week."After months of searching, you think you have a hit and then you go through the process of characterizing it -- is it new? Is it known? If it isn't, you have to start from square one. But when you do find something new like streptosactin, it's this rush of adrenaline that's unbelievable. That's why you go through the months of hard work. As a scientist, it's definitely what gets me into the lab every day."Even with a new search approach and an extremely sensitive instrument, streptosactin was difficult to identify from live cultures; its concentration was measured in the picomolar range.After bioinformatic prediction and characterization of the biosynthetic enzymes, Brett Covington, a postdoctoral researcher in the Seyedsayamdost lab, managed to pinpoint the molecule in bacterial culture extracts. He cultured the organism "in a medium that it likes," and used clever mass spectrometry tactics to locate the chemical fingerprints he was looking for."The problem we had with streptosactin is that, in lab cultures, it's not produced well at all. We have a really sensitive instrument and still, it's barely detectible over the noise," said Covington. "So for months I was looking at things, asking could they be noise or could they be real?"It's a roller coaster with natural products chemistry," Covington added. "If we had a little bit worse of an instrument, we wouldn't have found it. If we didn't concentrate it as well, we wouldn't have found it. If we didn't have the right types of methods that we were using, we wouldn't have seen it. You had to know exactly what you were looking for and you had to look for a really long time."Bushin said, "I truly believe Brett is one of only a few people in the world who could have completed this task."The properties and behavior of streptosactin have yet to be puzzled through: what is its role in the microbiome? Why the fratricidal behavior? And what other discoveries remain from the more than 600 natural products predicted by Bushin's search algorithm? These will form the basis of future research projects spearheaded by the Seyedsayamdost lab."There are multiple these projects that can be supported by this work," said Seyedsayamdost.
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Microbes
| 2,020 |
September 14, 2020
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https://www.sciencedaily.com/releases/2020/09/200914090710.htm
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Tiny antibody component highly effective against SARS-COV-2 in animal studies
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University of Pittsburgh School of Medicine scientists have isolated the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus, which is the cause of COVID-19. This antibody component, which is 10 times smaller than a full-sized antibody, has been used to construct a drug -- known as Ab8 -- for potential use as a therapeutic and prophylactic against SARS-CoV-2.
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The researchers report today in the journal Ab8 was evaluated in conjunction with scientists from the University of North Carolina at Chapel Hill (UNC) and University of Texas Medical Branch (UTMB) at Galveston, as well as the University of British Columbia and University of Saskatchewan."Ab8 not only has potential as therapy for COVID-19, but it also could be used to keep people from getting SARS-CoV-2 infections," said co-author John Mellors, M.D., chief of the Division of Infectious Diseases at UPMC and Pitt. "Antibodies of larger size have worked against other infectious diseases and have been well tolerated, giving us hope that it could be an effective treatment for patients with COVID-19 and for protection of those who have never had the infection and are not immune."The tiny antibody component is the variable, heavy chain (VH) domain of an immunoglobulin, which is a type of antibody found in the blood. It was found by "fishing" in a pool of more than 100 billion potential candidates using the SARS-CoV-2 spike protein as bait. Ab8 is created when the VH domain is fused to part of the immunoglobulin tail region, adding the immune functions of a full-size antibody without the bulk.Abound Bio, a newly formed UPMC-backed company, has licensed Ab8 for worldwide development.Dimiter Dimitrov, Ph.D., senior author of the Clinical trials are testing convalescent plasma -- which contains antibodies from people who already had COVID-19 -- as a treatment for those battling the infection, but there isn't enough plasma for those who might need it, and it isn't proven to work.That's why Dimitrov and his team set out to isolate the gene for one or more antibodies that block the SARS-CoV-2 virus, which would allow for mass production. In February, Wei Li, Ph.D., assistant director of Pitt's Center for Therapeutic Antibodies and co-lead author of the research, began sifting through large libraries of antibody components made using human blood samples and found multiple therapeutic antibody candidates, including Ab8, in record time.Then a team at UTMB's Center for Biodefense and Emerging Diseases and Galveston National Laboratory, led by Chien-Te Kent Tseng, Ph.D., tested Ab8 using live SARS-CoV-2 virus. At very low concentrations, Ab8 completely blocked the virus from entering cells. With those results in hand, Ralph Baric, Ph.D., and his UNC colleagues tested Ab8 at varying concentrations in mice using a modified version of SARS-CoV-2 . Even at the lowest dose, Ab8 decreased by 10-fold the amount of infectious virus in those mice compared to their untreated counterparts. Ab8 also was effective in treating and preventing SARS-CoV-2 infection in hamsters, as evaluated by Darryl Falzarano, Ph.D., and colleagues at the University of Saskatchewan. Sriram Subramaniam, Ph.D., and his colleagues at the University of British Columbia uncovered the unique way Ab8 neutralizes the virus so effectively by using sophisticated electron microscopic techniques."The COVID-19 pandemic is a global challenge facing humanity, but biomedical science and human ingenuity are likely to overcome it," said Mellors, also Distinguished Professor of Medicine, who holds the Endowed Chair for Global Elimination of HIV and AIDS at Pitt. "We hope that the antibodies we have discovered will contribute to that triumph."Additional co-lead authors of this research are Xianglei Liu, M.D., Ph.D., of Pitt; Alexandra Schäfer, Ph.D., and David R. Martinez, Ph.D., both of the University of North Carolina at Chapel Hill; and Swarali S. Kulkarni, M.Sc., of the University of Saskatchewan. Additional authors are Chuan Chen, Ph.D., Zehua Sun, Ph.D., Liyoung Zhang, Ph.D., all of Pitt; Sarah R. Leist, Ph.D., of the University of North Carolina at Chapel Hill; Aleksandra Drelich, Ph.D., of the University of Texas Medical Branch; Marcin L. Ura, Ph.D., and Eric Peterson, M.S., both of Abound Bio; and Alison Berezuk, Ph.D., Sagar Chittori, Ph.D., Karoline Leopold, Ph.D., Dhiraj Mannar, B.Sc., Shanti S. Srivastava, Ph.D., and Xing Zhu, Ph.D., all of the University of British Columbia.This research was funded by National Institutes of Health grants F32 AI152296, T32 AI007151, AI132178, AI108197 and P30CA016086, as well as UPMC; the Burroughs Wellcome Fund; a Canada Excellence Research Chair Award; Genome BC, Canada; Canadian Institutes for Health Research; and Canadian Foundation for Innovation.
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Microbes
| 2,020 |
September 11, 2020
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https://www.sciencedaily.com/releases/2020/09/200911093024.htm
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Uncovering the science of Indigenous fermentation
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Australian wine scientists are shedding scientific light on the processes underlying traditional practices of Australian Aboriginal people to produce fermented beverages.
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The scientists from the University of Adelaide and the Australian Wine Research Institute (AWRI) have discovered the complex microbial communities associated with the natural fermentation of sap from the iconic Tasmanian cider gum, Eucalyptus gunnii. The work has been published in the Nature journal The much-loved, but locally endangered, cider gum is native to the remote Central Plateau of Tasmania and also commonly planted as an ornamental tree across the British Isles and some parts of Western Europe."Cider gums produce a sweet sap that was collected by Aboriginal people to produce a mildly alcoholic beverage," says lead author Dr Cristian Varela, Principal Research Scientist with the AWRI."The drink known as way-a-linah was made by the Tasmanian Palawa people in a traditional practice where the sap was given time to spontaneously ferment."To the best of our knowledge, the microorganisms responsible for this traditional Australian fermentation have never been investigated or identified."The wine scientists, in collaboration with the Tasmanian Aboriginal Centre and the Tasmanian Land Conservancy, collected sap, bark and soil samples from around the cider gums in three locations in the Tasmanian Central Plateau.They used DNA sequencing to identify the bacterial and fungal communities they found. Some could not be matched to existing databases, suggesting they represent completely new classifications of bacteria and fungi, not previously described.Research leader Professor Vladimir Jiranek, Professor of Oenology with the University's School of Agriculture, Food and Wine, says: "The wider community is not typically aware of these historic traditions. This work shines a light on these practices and the cultural significance of these unique fermentations."It also allows us to identify new strains, or species, of yeast and bacteria from the fermentations that are unique to Australia. Further work will characterise single microorganisms that have been isolated and grown from the cider gum."We are particularly interested in their fermentative abilities, their potential flavour impacts, how they've adapted to the cider gum environment and the possible symbiotic relationship they have with the trees."We look forward to continuing our work with relevant Aboriginal communities in order to understand these and other processes, and help revive lost practices or perhaps develop new ones from these."
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Microbes
| 2,020 |
September 10, 2020
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https://www.sciencedaily.com/releases/2020/09/200910150336.htm
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Gut microbiome data may be helpful in routine screening of cardiovascular disease
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Using artificial intelligence to analyze the bacteria in a person's gut microbiome shows promise as a new screening method for cardiovascular disease (CVD), according to preliminary research to be presented Sept. 10-13, 2020, at the virtual American Heart Association's Hypertension 2020 Scientific Sessions. The meeting is a premier global exchange for clinical and basic researchers focusing on recent advances in hypertension research. The full study published simultaneously today in Hypertension, an American Heart Association journal.
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Recent studies have found a link between gut microbiota, the microorganisms in human digestive tracts, and CVD, which is the leading cause of mortality worldwide. Gut microbiota is highly variable between individuals, and differences in gut microbial compositions between people with and without CVD have been reported."Based on our previous research linking gut microbiota to CVD in animal models, we designed this study to test whether it is possible to screen for CVD in humans using artificial intelligence screening of stool samples," said Bina Joe, Ph.D., FAHA, the study director, Distinguished University Professor and Chairwoman of the department of physiology and pharmacology at the University of Toledo in Toledo, Ohio. "Gut microbiota has a profound effect on cardiovascular function, and this could be a potential new strategy for evaluation of cardiovascular health."Researchers used data from the American Gut Project (an open platform for microbiome research based in the United States) to analyze microbial composition of stool samples with state-of-the-art machine learning modeling. Nearly 1,000 samples were analyzed, and approximately half of the samples were from people with CVD. The model was able to identify different clusters of gut bacteria that could potentially help identify individuals with existing CVD and without CVD.Among the bacteria identified:Bacteroides, Subdoligranulum, Clostridium, Megasphaera, Eubacterium, Veillonella, Acidaminococcus and Listeria were more abundant in the CVD group.Faecalibacterium, Ruminococcus, Proteus, Lachnospira, Brevundimonas, Alistipes and Neisseria were more abundant in the non-CVD group."Despite the fact that gut microbiomes are highly variable among individuals, we were surprised by the promising level of accuracy obtained from these preliminary results, which indicate fecal microbiota composition could potentially serve as a convenient diagnostic screening method for CVD," Joe said. "It is conceivable that one day, maybe without even assessing detailed cardiovascular function, clinicians could analyze the gut microbiome of patients' stool samples with an artificial machine learning method to screen patients for heart and vascular diseases."
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Microbes
| 2,020 |
September 10, 2020
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https://www.sciencedaily.com/releases/2020/09/200910110850.htm
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Human norovirus strains differ in sensitivity to the body's first line of defense
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Interferon (IFN) responses are one of the first defenses the body mounts against viral infections, and research has shown that it plays a role controlling viral replication. But when researchers at Baylor College of Medicine investigated whether IFN restricted human norovirus (HuNoV) infection in human intestinal enteroids (HIEs), a cultivation system that recapitulates many of the characteristics of the human infection, they unexpectedly discovered that endogenous IFN responses by HIEs restricted growth of HuNoV strain GII.3, but not of GII.4, the most common strain worldwide.
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The findings, published in the "HuNoVs cause the majority of the cases of viral gastroenteritis in the world and bring about significant mortality in all age groups; yet, there are still no vaccines or other approved therapeutic strategies available," said first author Shih-Ching Lin, a graduate student in the laboratory of Dr. Mary Estes at Baylor. "In-depth studies of how virus and host interact have been possible only recently thanks to the development of several laboratory cultivation systems. In this study, we worked with HIEs to investigate their response to HuNoV infection and how it affects viral replication."The researchers infected HIEs with HuNoV strain GII.3 or pandemic strain GII.4 and determined which HIE genes were activated as a result."We discovered that both strains preferentially triggered a type III IFN response, including activation of a number of IFN-stimulated genes, as well as increases in a subset of long non-coding RNAs. Changes in long non-coding RNAs, which are known to regulate gene expression, had never been reported before for gastrointestinal virus infections," Lin said.Next, Lin, Estes and their colleagues studied the effect of IFN on the replication of HuNoV. Adding IFN to the cultures reduced replication of both strains, suggesting that IFN may have value as therapeutics for HuNoV infections. This could be important for chronically infected immunocompromised patients who can suffer with diarrhea for years.To obtain insights into the genes of the IFN pathway that contribute to the antiviral response to HuNoV, the researchers knocked out several of these genes in HIE cultures, infected them with strain GII.3 or GII.4 and measured the rate of viral proliferation."We expected that the absence of IFN responses by HIEs would promote viral replication in both strains. It was surprising and very exciting to find significant strain differences," Lin said."We saw that only strain GII.3 was able to spread and multiply more when HIEs could not activate IFN responses. Replication of GII.4, on the other hand, was not enhanced," said Estes, Cullen Foundation Endowed Chair and Distinguished Service Professor of molecular virology and microbiology at Baylor. Estes also is a member of the Dan L Duncan Comprehensive Cancer Center. "It was exciting to see the GII.3 strain proliferate and spread in the cultures as we had never seen it before.""The strain-specific sensitivities of innate IFN responses to HuNoV replication we observed provide a potential explanation for why GII.4 infections are more widespread and become pandemic," Lin said. "Our findings also show the importance of keeping potential strain differences in mind when studying the biology of HuNoV and developing therapies. Our new genetically modified HIE cultures also will be useful tools for studying innate immune responses to other viral or microbial pathogens."
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Microbes
| 2,020 |
September 10, 2020
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https://www.sciencedaily.com/releases/2020/09/200910110839.htm
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Anti-bacterial graphene face masks
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Face masks have become an important tool in fighting against the COVID-19 pandemic. However, improper use or disposal of masks may lead to "secondary transmission." A research team from City University of Hong Kong (CityU) has successfully produced graphene masks with an anti-bacterial efficiency of 80%, which can be enhanced to almost 100% with exposure to sunlight for around 10 minutes. Initial tests also showed very promising results in the deactivation of two species of coronaviruses. The graphene masks are easily produced at low cost, and can help to resolve the problems of sourcing raw materials and disposing of non-biodegradable masks.
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The research is conducted by Dr Ye Ruquan, Assistant Professor from CityU's Department of Chemistry, in collaboration with other researchers. The findings were published in the scientific journal Commonly used surgical masks are not anti-bacterial. This may lead to the risk of secondary transmission of bacterial infection when people touch the contaminated surfaces of the used masks or discard them improperly. Moreover, the melt-blown fabrics used as a bacterial filter poses an impact on the environment as they are difficult to decompose. Therefore, scientists have been looking for alternative materials to make masks.Dr Ye has been studying the use of laser-induced graphene in developing sustainable energy. When he was studying PhD degree at Rice University several years ago, the research team he participated in and led by his supervisor discovered an easy way to produce graphene. They found that direct writing on carbon-containing polyimide films (a polymeric plastic material with high thermal stability) using a commercial COGraphene is known for its anti-bacterial properties, so as early as last September, before the outbreak of COVID-19, producing outperforming masks with laser-induced graphene already came across Dr Ye's mind. He then kick-started the study in collaboration with researchers from the Hong Kong University of Science and Technology (HKUST), Nankai University, and other organisations.The research team tested their laser-induced graphene with E. coli, and it achieved high anti-bacterial efficiency of about 82%. In comparison, the anti-bacterial efficiency of activated carbon fibre and melt-blown fabrics, both commonly-used materials in masks, were only 2% and 9% respectively. Experiment results also showed that over 90% of the E. coli deposited on them remained alive even after 8 hours, while most of the E. coli deposited on the graphene surface were dead after 8 hours. Moreover, the laser-induced graphene showed a superior anti-bacterial capacity for aerosolised bacteria.Dr Ye said that more research on the exact mechanism of graphene's bacteria-killing property is needed. But he believed it might be related to the damage of bacterial cell membranes by graphene's sharp edge. And the bacteria may be killed by dehydration induced by the hydrophobic (water-repelling) property of graphene.Previous studies suggested that COVID-19 would lose its infectivity at high temperatures. So the team carried out experiments to test if the graphene's photothermal effect (producing heat after absorbing light) can enhance the anti-bacterial effect. The results showed that the anti-bacterial efficiency of the graphene material could be improved to 99.998% within 10 minutes under sunlight, while activated carbon fibre and melt-blown fabrics only showed an efficiency of 67% and 85% respectively.The team is currently working with laboratories in mainland China to test the graphene material with two species of human coronaviruses. Initial tests showed that it inactivated over 90% of the virus in five minutes and almost 100% in 10 minutes under sunlight. The team plans to conduct testings with the COVID-19 virus later.Their next step is to further enhance the anti-virus efficiency and develop a reusable strategy for the mask. They hope to release it to the market shortly after designing an optimal structure for the mask and obtaining the certifications.Dr Ye described the production of laser-induced graphene as a "green technique." All carbon-containing materials, such as cellulose or paper, can be converted into graphene using this technique. And the conversion can be carried out under ambient conditions without using chemicals other than the raw materials, nor causing pollution. And the energy consumption is low."Laser-induced graphene masks are reusable. If biomaterials are used for producing graphene, it can help to resolve the problem of sourcing raw material for masks. And it can lessen the environmental impact caused by the non-biodegradable disposable masks," he added.Dr Ye pointed out that producing laser-induced graphene is easy. Within just one and a half minutes, an area of 100 cm² can be converted into graphene as the outer or inner layer of the mask. Depending on the raw materials for producing the graphene, the price of the laser-induced graphene mask is expected to be between that of surgical mask and N95 mask. He added that by adjusting laser power, the size of the pores of the graphene material can be modified so that the breathability would be similar to surgical masks.To facilitate users to check whether graphene masks are still in good condition after being used for a period of time, the team fabricated a hygroelectric generator. It is powered by electricity generated from the moisture in human breath. By measuring the change in the moisture-induced voltage when the user breathes through a graphene mask, it provides an indicator of the condition of the mask. Experiment results showed that the more the bacteria and atmospheric particles accumulated on the surface of the mask, the lower the voltage resulted. "The standard of how frequently a mask should be changed is better to be decided by the professionals. Yet, this method we used may serve as a reference," suggested Dr Ye.Dr Ye is one of the corresponding authors of the paper. The other two corresponding authors are Professor Tang Benzhong from HKUST, and Dr Zhu Chunlei from Nankai University. The first author of the paper is Huang Libei, Dr Ye's PhD student. Other CityU team members are Xu Siyu, Su Jianjun, and Song Yun, all from the Department of Chemistry. Other collaborators included researchers from HKUST, Nankai University, as well as Dr Chen Sijie of the Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet.The study was supported by CityU and Nankai University.
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Microbes
| 2,020 |
September 6, 2020
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https://www.sciencedaily.com/releases/2020/09/200906135310.htm
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Common cold jumpstarts defense against influenza
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As the flu season approaches, a strained public health system may have a surprising ally -- the common cold virus.
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Rhinovirus, the most frequent cause of common colds, can prevent the flu virus from infecting airways by jumpstarting the body's antiviral defenses, Yale researchers report Sept. 4 in the journal The findings help answer a mystery surrounding the 2009 H1N1 swine flu pandemic: An expected surge in swine flu cases never materialized in Europe during the fall, a period when the common cold becomes widespread.A Yale team led by Dr. Ellen Foxman studied three years of clinical data from more than 13,000 patients seen at Yale New Haven Hospital with symptoms of respiratory infection. The researchers found that even during months when both viruses were active, if the common cold virus was present, the flu virus was not."When we looked at the data, it became clear that very few people had both viruses at the same time," said Foxman, assistant professor of laboratory medicine and immunobiology and senior author of the study.Foxman stressed that scientists do not know whether the annual seasonal spread of the common cold virus will have a similar impact on infection rates of those exposed to the coronavirus that causes COVID-19."It is impossible to predict how two viruses will interact without doing the research," she said.To test how the rhinovirus and the influenza virus interact, Foxman's lab created human airway tissue from stem cells that give rise to epithelial cells, which line the airways of the lung and are a chief target of respiratory viruses. They found that after the tissue had been exposed to rhinovirus, the influenza virus was unable to infect the tissue."The antiviral defenses were already turned on before the flu virus arrived," she said.The presence of rhinovirus triggered production of the antiviral agent interferon, which is part of the early immune system response to invasion of pathogens, Foxman said."The effect lasted for at least five days," she said.Foxman said her lab has begun to study whether introduction of the cold virus before infection by the COVID-19 virus offers a similar type of protection.
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Microbes
| 2,020 |
September 3, 2020
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https://www.sciencedaily.com/releases/2020/09/200903115735.htm
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How to capture images of cells at work inside our lungs
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University of Calgary scientists have discovered how to capture "live" images of immune cells inside the lungs. The group at the Snyder Institute for Chronic Diseases at the Cumming School of Medicine is the first in the world to find a way to record, in real time, how the immune system battles bacteria impacting the alveoli, or air sacs, in the lungs of mice. The discovery has already provided new insights about the immune systems' cleaners, called alveolar macrophages. Once thought to be stationary, the scientists observed the macrophages at work, crawling over, between and around the alveolar spaces in search of bacteria and viruses.
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"It makes sense that macrophages would move around, but we could only hypothesise this because we couldn't see them in action. Now we can," says Dr. Paul Kubes, PhD, principal investigator. "There are many more alveoli in the lungs than macrophages, and these tiny cleaners are very efficient at servicing every air sac."The researchers say the job the macrophages do is quite simple. Think of a hotel, where there are more rooms than cleaning staff. The staff use hallways to clean and keep things in order. Inside the lungs, there is a corridor that provides a space between the alveoli. The macrophages use this space to move around to destroy any foreign particles including bacteria and viruses impacting the air sacs.The scientists needed to conquer three major obstacles in order to capture live images of this immune cell at work. The team needed to develop a way to capture an image from air to liquid to air again, they needed to stabilize the lungs long enough to get a clear picture, and they needed to find a way to identify and mark the macrophages."This work is a culmination of years of research by scientists around the world. We pulled everything together, combining and refining many imaging techniques," says Arpan Neupane, PhD candidate and first author on the study. "Even six years ago, this would not have been possible."The ability to see macrophages at work has revealed something else: the scientists watched as the powerful cleaners became paralyzed and stopped doing their important job."We know when someone is battling a serious infection, especially a respiratory virus like flu or COVID-19, they often develop a secondary infection which can lead to death," says Kubes. "With this new imaging technique, we were able to see what's happening with the macrophages during this process."It turns out, at a certain point during the battle against infections, the efficient cleaners become paralyzed making it easier for new infections to take root and flourish."The next step in our research is to find out why this is happening so that we can develop targeted therapies to kick start the macrophages into action again," says Kubes.Findings from the study are published in
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Microbes
| 2,020 |
September 3, 2020
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https://www.sciencedaily.com/releases/2020/09/200903114206.htm
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Antibiotics affect breast milk microbiota in mothers of preterm infants, study finds
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A team led by researchers at the University of Toronto and The Hospital for Sick Children has found that mothers of preterm babies have highly individual breast milk microbiomes, and that even short courses of antibiotics have prolonged effects on the diversity and abundance of microbes in their milk.
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The study is the largest to date of breast milk microbiota in mothers of preterm infants, and it is the first to show that antibiotic class, timing and duration of exposure have particular effects on the most common microbes in breast milk -- many of which have the potential to influence growth and immunity to disease in newborns."It came as quite a shock to us that even one day of antibiotics was associated with profound changes in the microbiota of breast milk," says Deborah O'Connor, who is a professor and chair of nutritional sciences at U of T and a senior associate scientist at SickKids. "I think the take-home is that while antibiotics are often an essential treatment for mothers of preterm infants, clinicians and patients should be judicious in their use."Most antibiotic stewardship programs in neonatal intensive care focus on limiting use in newborns themselves. The current study adds to growing evidence that these programs should include a focus on mothers as well, says O'Connor, principal investigator on the study who is also a scientist in the Joannah & Brian Lawson Centre for Child Nutrition.The journal The researchers looked at 490 breast milk samples from 86 mothers whose infants were born preterm, during the first eight weeks after delivery. They found that the mothers' body mass index and mode of delivery influenced the breast milk microbiota, consistent with some other studies.But the effects of antibiotics were the most pronounced, and in some cases they lasted for weeks. Many of the antibiotic-induced changes affected key microbes known to play a role in fostering disease, or in gut health and metabolic processes that promote babies' growth and development."Overall we saw a decrease in metabolic pathways, and increase in more pathogenic pathways in bacteria over time," says Michelle Asbury, a doctoral student in O'Connor's lab and lead author on the paper. "Of particular concern was an association between antibiotics and a member of the Proteobacteria phylum called Pseudomonas. When elevated, Proteobacteria in a preterm infant's gut can precede necrotizing enterocolitis."About seven per cent of babies born preterm develop necrotizing enterocolitis, a frequently fatal condition in which part of the bowel dies. A class of antibiotics called cephalosporins also had a big effect on the overall diversity of breast milk microbiota.Asbury says it is too early to know what the findings mean for preterm infant health and outcomes. She and her colleagues will dive into those questions over the next year, as they compare their findings with stool samples from the preterm infants involved in the study. This should reveal whether changes in the mothers' milk microbiomes are actually seeding the infants' guts to promote health or increase disease risk.Meanwhile, she says it's important that mothers with preterm infants continue to take antibiotics for some cases of mastitis, blood infections and early rupture of membranes. Roughly 60 per cent of women in the current study took antibiotics -- highlighting both the vast need for these drugs and the potential for some overuse.Sharon Unger is a co-author on the study and a professor of paediatrics at U of T, as well as a scientist and neonatologist at Sinai Health and SickKids. She says that the benefits of breast feeding far outweigh the risk that antibiotics can disrupt the breast milk microbiome, and that mothers should without question continue to provide their own milk when possible."But I think we can look to narrow the spectrum of antibiotics we use and to shorten the duration when possible," Unger says. She adds that advances in technology may allow for quicker diagnoses of infection and better antibiotic stewardship in the future.As for the rapidly moving field of microbiome research, Unger says it holds great promise for preterm infants. "Clearly the microbiome is important for their metabolism, growth and immunity. But emerging evidence on the gut-brain axis and its potential to further improve neurodevelopment for these babies over the long term warps my mind."
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Microbes
| 2,020 |
September 3, 2020
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https://www.sciencedaily.com/releases/2020/09/200903075910.htm
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Wearable, portable invention offers options for treating antibiotic-resistant infections
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The rapid increase of life-threatening antibiotic-resistant infections has resulted in challenging wound complications with limited choices of effective treatments. About 6 million people in the United States are affected by chronic wounds.
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Now, a team of innovators from Purdue University has developed a wearable solution that allows a patient to receive treatment without leaving home. The Purdue team's work is published in the journal A video showing the technology is available at "We created a revolutionary type of treatment to kill the bacteria on the surface of the wound or diabetic ulcer and accelerate the healing process," said Rahim Rahimi, an assistant professor of materials engineering at Purdue. "We created a low-cost wearable patch and accompanying components to deliver ozone therapy."Ozone therapy is a gas phase antimicrobial treatment option that is being used by a growing number of patients in the U.S. In most cases, the ozone treatments require patients to travel to a clinical setting for treatment by trained technicians."Our breathable patch is applied to the wound and then connected to a small, battery powered ozone-generating device," Rahimi said. "The ozone gas is transported to the skin surface at the wound site and provides a targeted approach for wound healing. Our innovation is small and simple to use for patients at home."The team worked with the Purdue Research Foundation Office of Technology Commercialization to patent the technology.The creators are looking for partners to continue developing their technology.
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Microbes
| 2,020 |
September 2, 2020
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https://www.sciencedaily.com/releases/2020/09/200902114455.htm
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Inflammation linked to Alzheimer's disease development
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Alzheimer's disease is a neurodegenerative condition that is characterized by the buildup of clumps of beta-amyloid protein in the brain. Exactly what causes these clumps, known as plaques, and what role they play in disease progression is an active area of research important for developing prevention and treatment strategies.
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Recent studies have found that beta-amyloid has antiviral and antimicrobial properties, suggesting a possible link between the immune response against infections and the development of Alzheimer's disease.Chemical biologists at the Sloan Kettering Institute have now discovered clear evidence of this link: A protein called IFITM3 that is involved in the immune response to pathogens also plays a key role in the accumulation of beta-amyloid in plaques."We've known that the immune system plays a role in Alzheimer's disease -- for example, it helps to clean up beta-amyloid plaques in the brain," says Yue-Ming Li, a chemical biologist at SKI. "But this is the first direct evidence that immune response contributes to the production of beta-amyloid plaques -- the defining feature of Alzheimer's disease."In a paper published September 2 in They found that removing IFITM3 decreased the activity of the gamma-secretase enzyme and, as a result, reduced that number of amyloid plaques that formed in a mouse model of the disease.Neuroinflammation, or inflammation in the brain, has emerged as an important line of inquiry in Alzheimer's disease research. Markers of inflammation, such as certain immune molecules called cytokines, are boosted in Alzheimer's disease mouse models and in the brains of people with Alzheimer's disease. Dr. Li's study is the first to provide a direct link between this inflammation and plaque development -- by way of IFITM3.Scientists know that the production of IFITM3 starts in response to activation of the immune system by invading viruses and bacteria. These observations, combined with the new findings from Dr. Li's lab that IFITM3 directly contributes to plaque formation, suggest that viral and bacterial infections could increase the risk of Alzheimer's disease development. Indeed, Dr. Li and his colleagues found that the level of IFITM3 in human brain samples correlated with levels of certain viral infections as well as with gamma-secretase activity and beta-amyloid production.Age is the number one risk factor for Alzheimer's, and the levels of both inflammatory markers and IFITM3 increased with advancing age in mice, the researchers found.They also discovered that IFITM3 is increased in a subset of late onset Alzheimer's patients, meaning that IFITM3 could potentially be used as a biomarker to identify a subset of patients who might benefit from therapies targeted against IFITM3.The researchers next plan is to investigate how IFITM3 interacts with gamma-secretase at the molecular and atomic levels and how it is involved in neuroinflammation in animal models. They will also explore IFITM3 as a biomarker for the disease and as a potential target for new drugs designed to treat it.
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Microbes
| 2,020 |
August 31, 2020
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https://www.sciencedaily.com/releases/2020/08/200831112347.htm
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Insight on how to build a better flu vaccine
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Flu season comes around like clockwork every year, and sooner or later everyone gets infected. The annual flu shot is a key part of public health efforts to control the flu, but the vaccine's effectiveness is notoriously poor, falling somewhere from 40% to 60% in a typical year.
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A growing body of evidence suggests that a history of exposure to influenza virus might be undermining the effectiveness of the annual flu vaccine. Partial immunity developed during prior flu seasons -- either through natural infection or vaccination -- might interfere with the body's response to a new vaccine, such that vaccination mainly boosts the recognition of prior influenza strains but does little to create the ability to fight new strains.Now, a team led by researchers at Washington University School of Medicine in St. Louis has developed an approach to assess whether a vaccine activates the kind of immune cells needed for long-lasting immunity against new influenza strains. Using this technique, the researchers showed that the flu vaccine is capable of eliciting antibodies that protect against a broad range of flu viruses, at least in some people. The findings, published Aug. 31 in the journal "Every year, about half of the U.S. adult population gets vaccinated against influenza," said senior author Ali Ellebedy, PhD, an assistant professor of pathology and immunology at Washington University. "It's necessary for public health, but it's also incredibly expensive and inefficient. What we need is a one-and-done influenza shot, but we are not there yet. Anything that helps us understand how immunity develops in the context of prior exposures would be important as we try to make a better vaccine."The key to long-lasting immunity lies in lymph nodes, minuscule organs of the immune system positioned throughout the body. Easy to miss in healthy people, lymph nodes become swollen and tender during an infection as immune cells busily interact and multiply within them.The first time a person is exposed to a virus -- either by infection or vaccination -- immune cells capture the virus and bring it to the nearest lymph node. There, the virus is presented to so-called naïve B cells, causing them to mature and start producing antibodies to fight the infection. Once the virus is successfully routed, most of the immune cells that take part in the battle die off, but a few continue circulating in the blood as long-lived memory B cells.The second time a person is exposed to a virus, memory B cells quickly reactivate and start producing antibodies again, bypassing naive B cells. This rapid response quickly builds protection for people who have been reinfected with the exact same strain of virus, but it's not ideal for people who have received a vaccine designed to build immunity against a slightly different strain, as in the annual flu vaccine."If our influenza vaccine targets memory cells, those cells will respond to the parts of the virus that haven't changed from previous influenza strains," Ellebedy said. "Our goal is to get our immune system up to date with the new strains of influenza, which means we want to focus the immune response on the parts of the virus that are different this year."To get decades-long immunity against the new strains, the flu strains from the vaccine need to be taken to the lymph nodes, where they can be used to train a new set of naïve B cells and induce long-lived memory B cells specifically tailored to recognize the unique features of the vaccine strains.To find out what happens inside lymph nodes after influenza vaccination, Ellebedy enlisted the help of co-authors Rachel Presti, MD, PhD, an associate professor of medicine, and Sharlene Teefey, MD, a professor of radiology at Washington University. Presti led a team at the Infectious Disease Clinical Research Unit that coordinated the sampling of blood and lymph nodes from healthy volunteers before and after vaccination. Guided by ultrasound imaging, Teefey carefully extracted so-called germinal centers that hold immune cells from underarm lymph nodes of eight healthy, young volunteers vaccinated with the 2018-19 quadrivalent influenza vaccine. That vaccine was designed to protect against four different strains of influenza virus. The immune cells were extracted at one, two, four and nine weeks after vaccination.Ellebedy and colleagues - including co-senior authors Steven Kleinstein, PhD, a professor of pathology at Yale University School of Medicine, and Andrew Ward, PhD, a professor of integrative structural and computational biology at Scripps Research Institute, as well as co-first authors Jackson Turner, PhD, a postdoctoral researcher who works with Ellebedy, Julian Zhou, a graduate student in Kleinstein's lab, and Julianna Han, PhD, a postdoctoral scholar who works with Ward -- analyzed the immune cells in the germinal centers to find the ones that had been activated by vaccination.In three volunteers, both memory B cells and naïve B cells in the lymph nodes responded to the vaccine strains, indicating that the vaccine had initiated the process of inducing long-lasting immunity against the new strains."Our study shows that the influenza vaccine can engage both kinds of cells in the germinal centers, but we still don't know how often that happens," Ellebedy said. "But given that influenza vaccine effectiveness hovers around 50%, it probably doesn't happen as often as we would like. That brings up the importance of promoting strategies to boost the germinal centers as a step toward a universal influenza vaccine."
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Microbes
| 2,020 |
August 28, 2020
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https://www.sciencedaily.com/releases/2020/08/200828115336.htm
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Preventing infection, facilitating healing: New biomaterials from spider silk
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New biomaterials developed at the University of Bayreuth may eliminate the risk of infection and facilitate healing processes. A research team led by Prof. Dr. Thomas Scheibel has succeeded in combining these material properties which are highly relevant to biomedicine. These nanostructured materials are based on spider silk proteins. They prevent colonization by bacteria and fungi, but at the same time proactively assist in the regeneration of human tissue. They are therefore ideal for implants, wound dressings, prostheses, contact lenses, and other everyday aids. The scientists have presented their innovation in the journal
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It is a widely underestimated risk of infection: Microbes settling on the surfaces of objects indispensable in medical therapy or for quality of life generally. Gradually, they form a dense, often invisible biofilm that cannot be easily removed, even by cleaning agents, and which often is resistant against antibiotics and antimycotics. Bacteria and fungi can then migrate into the adjacent tissue of the organism. As a result, they not only interfere with various processes of healing, but can even cause life-threatening infections.With a novel research approach, University of Bayreuth scientists have now found a solution to this problem. Using biotechnologically produced spider silk proteins, they have developed a material that prevents the adhesion of pathogenic microbes. Even streptococci, resistant to multiple antibacterial agents (MRSA), have no chance of settling on the material surface. Biofilms growing on medical instruments, sports equipment, contact lenses, prostheses, and other everyday objects may therefore soon be history.Moreover, the materials are designed to simultaneously aid the adhesion and proliferation of human cells on their surface. If they can be used for e.g. wound dressings, skin replacement, or implants, they proactively support the regeneration of damaged or lost tissue. In contrast to other materials that have previously been used to regenerate tissue, the risk of infection is intrinsically eliminated. Microbial-resistant coatings for a variety of biomedical and technical applications are thus set to become available in the near future.The Bayreuth researchers have so far successfully tested the microbe-repellent function on two types of spider silk materials: on films and coatings that are only a few nanometres thick and on three-dimensional hydrogel scaffolds which can serve as precursors for tissue regeneration. "Our investigations to date have led to a finding that is absolutely ground-breaking for future research work. In particular, the microbe-repellent properties of the biomaterials we have developed are not based on toxic, i.e. not cell-destroying, effects. The decisive factor rather lies in structures at the nanometre level, which make the spider silk surfaces microbe-repellent. They make it impossible for pathogens to attach themselves to these surfaces," explains Prof. Dr. Thomas Scheibel, who is the Chair of Biomaterials at the University of Bayreuth."Another fascinating aspect is that nature has once again proven to be the ideal role model for highly advanced material concepts. Natural spider silk is highly resistant to microbial infestation and the reproduction of these properties in a biotechnological way is a break-through," adds Prof. Dr.-Ing. Gregor Lang, one of the two first authors and head of the research group of Biopolymer Processing at the University of Bayreuth.In the Bayreuth laboratories, spider silk proteins were specifically designed with various nanostructures in order to optimize biomedically relevant properties for specific applications. Once again, the networked research facilities on the Bayreuth campus have proven their worth. Together with the Bavarian Polymer Institute (BPI), three other interdisciplinary research institutes of the University of Bayreuth were involved in this research breakthrough: the Bayreuth Centre for Material Science & Engineering (BayMAT), the Bayreuth Centre for Colloids & Interfaces (BZKG), and the Bayreuth Centre for Molecular Biosciences (BZKG).
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Microbes
| 2,020 |
August 27, 2020
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https://www.sciencedaily.com/releases/2020/08/200827141331.htm
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Microbes working together multiply biomass conversion possibilities
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With the race for renewable energy sources in full swing, plants offer one of the most promising candidates for replacing crude oil. Lignocellulose in particular -- biomass from non-edible plants like grass, leaves, and wood that don't compete with food crops -- is abundant and renewable and offers a great alternative source to petroleum for a whole range of chemicals.
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In order to extract useful chemicals from it, lignocellulose is first pretreated to "break it up" and make it easier to further process. Then it's exposed to enzymes that solubilize cellulose, which is a chain of linked up sugars (glucose). This step can be done by adding to the pre-treated lignocellulose a microorganism that naturally produces the necessary, cellulose-cleaving enzymes, e.g. a fungus.The enzymes "crack" the cellulose and turn it into its individual sugars, which can be further processed to produce a key chemical: lactic acid. This second step is also accomplished with a microorganism, a bacterium that "eats" the sugars and produces lactic acid when there's no oxygen around.In the final step of this microbial assembly line, the lactic acid can then be processed to make a whole host of useful chemicals.A team of scientists from the Bern University of Applied Sciences (BFH), the University of Cambridge, and EPFL have made this assembly chain possible in a single setup and demonstrated this conversion can be made more versatile and modular. By easily swapping out the microorganisms in the final, lactic-acid processing, step, they can produce a whole range of useful chemicals.The breakthrough study is published in The researchers present what they refer to as a "lactate platform," which is essentially a spatially segregated bioreactor that allows multiple different microorganisms to co-exist, each performing one of the three steps of lignocellulose processing.The platform consists of a tubular membrane that lets a defined amount of oxygen to go through it. On the tube's surface can be grown the fungus that consumes all oxygen that passes through the membrane, and provides the enzymes that will break up cellulose into sugars. Further away from the membrane, and therefore in an atmosphere without oxygen, grow the bacteria that will "eat" the sugars and turn them into lactic acid.But the innovation that Shahab made was in the last step. By using different lactic acid-fermenting microorganisms, he was able to produce different useful chemicals. One example was butyric acid, which can be used in bioplastics, while Luterbacher's lab recently showed that it can even be turned into a jet fuel.The work demonstrates the benefits of mixed microbial cultures in lignocellulose biomass processing: modularity and the ability to convert complex substrates to valuable platform chemicals."The results achieved with the lactate platform nicely show the advantages of artificial microbial consortia to form new products from lignocellulose," says Michael Studer. "The creation of niches in otherwise homogeneous bioreactors is a valuable tool to co-cultivate different microorganisms.""Fermenting lignocellulose to a lot of different products was a significant amount of work but it was important to show how versatile the lactate platform is," says Robert Shahab. "To see the formation of lactate and the conversion into target products was a great experience as it showed that the concept of the lactate platform worked in practice."Jeremy Luterbacher adds: "The ultimate goal is to rebuild a green manufacturing sector to replace one that produces many products from crude oil. A method that introduces flexibility and modularity is an important step in that direction."
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Microbes
| 2,020 |
August 27, 2020
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https://www.sciencedaily.com/releases/2020/08/200827141303.htm
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A new method for making a key component of plastics
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Scientists have discovered a previously unknown way that some bacteria produce the chemical ethylene -- a finding that could lead to new ways to produce plastics without using fossil fuels.
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The study, published today (Aug. 27, 2020) in the journal But the process that the bacteria use to do that could make it very valuable in manufacturing, said Justin North, lead author of the study and a research scientist in microbiology at The Ohio State University."We may have cracked a major technological barrier to producing a large amount of ethylene gas that could replace fossil fuel sources in making plastics," North said."There's still a lot of work to do to develop these strains of bacteria to produce industrially significant quantities of ethylene gas. But this opens the door."Researchers from Ohio State worked on the study with colleagues from Colorado State University, Oak Ridge National Laboratory and the Pacific Northwest National Laboratory.Ethylene is widely used in the chemical industry to make nearly all plastics, North said. It is used more than any other organic compound in manufacturing.Currently, oil or natural gas are used to create ethylene. Other researchers have discovered bacteria that can also create the chemical, but there had been a technological barrier to using it -- the need for oxygen as part of the process, said Robert Tabita, senior author of the study and professor of microbiology at Ohio State."Oxygen plus ethylene is explosive, and that is a major hurdle for using it in manufacturing," said Tabita, who is an Ohio Eminent Scholar."But the bacterial system we discovered to produce ethylene works without oxygen and that gives us a significant technological advantage."The discovery was made in Tabita's lab at Ohio State when researchers were studying Rhodospirillum rubrum bacteria. They noticed that the bacteria were acquiring the sulfur they needed to grow from methylthio ethanol."We were trying to understand how the bacteria were doing this, because there were no known chemical reactions for how this was occurring," North said.That was when he decided to see what gases the bacteria were producing -- and discovered ethylene gas was among them.Working with colleagues from Colorado State and the two national labs, North, Tabita and other Ohio State colleagues were able to identify the previously unknown process that liberated the sulfur the bacteria needed, along with what North called the "happy byproduct" of ethylene.That wasn't all: The researchers also discovered the bacteria were using dimethyl sulfide to create methane, a potent greenhouse gas.All the research was done in the lab, so it remains to be seen exactly how common this process is in the environment, North said.But the researchers have identified one situation where this newly discovered process of ethylene production may have real-life consequences.Ethylene is an important natural plant hormone that, in the right amounts, is key to the growth and health of plants. But it is also harmful to plant growth in high quantities, said study co-author Kelly Wrighton, associate professor of soil and crop science at Colorado State University."This newly discovered pathway may shed light on many previously unexplained environmental phenomena, including the large amounts of ethylene that accumulates to inhibitory levels in waterlogged soils, causing extensive crop damage," Wrighton said.Added North: "Now that we know how it happens, we may be able to circumvent or treat these problems so that ethylene doesn't accumulate in soils when flooding occurs."Tabita said this research is the result of a happy accident."This study, involving the collaborative research and expertise of two universities and two national laboratories, is a perfect example of how serendipitous findings often lead to important advances," Tabita said."Initially, our studies involved a totally unrelated research problem that had seemingly no relationship to the findings reported here."While studying the role of one particular protein in bacteria sulfur metabolism, the researchers noted an entirely different group of proteins were unexpectedly involved as well. This led to the discovery of novel metabolic reactions and the unexpected production of large quantities of ethylene."It was a result we could not predict in a million years," Tabita said."Recognizing the industrial and environmental significance of ethylene, we embarked on these cooperative studies, and subsequently discovered a completely novel complex enzyme system. Who would have believed it?"The research was supported by the Department of Energy's Office of Science, the National Cancer Institute and the National Science Foundation.
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Microbes
| 2,020 |
August 27, 2020
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https://www.sciencedaily.com/releases/2020/08/200827141250.htm
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Prior Zika virus infection increases risk of severe dengue disease
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Getting sick with the mosquito-borne Zika virus makes people more vulnerable to developing dengue disease later on, and to suffering from more severe symptoms when they do get sick from dengue, finds a new study published online today (Thursday, Aug. 27) in the journal
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The study, which drew on data from two cohorts of Nicaraguan children who lived through a Zika epidemic in 2016 and a dengue epidemic in 2019, is the first to investigate the impacts of Zika immunity on dengue disease in humans.Its findings confirm earlier suspicions that some antibodies to the Zika virus, which usually serve to protect the body from infection, may actually interact with dengue viruses in ways that can make dengue infection worse. This interaction, known as antibody-dependent enhancement, could make it harder for researchers to design a safe and effective vaccine that protects against Zika without also increasing the risk of dengue."The key thing that our study establishes is that prior Zika infection does significantly increase your risk of both symptomatic and more severe forms of dengue disease," said study first author Leah Katzelnick, who performed the research as postdoctoral scholar at the University of California, Berkeley's School of Public Health. "That finding raises the questions: Could a vaccine only targeted at Zika actually put people at increased risk of more severe dengue disease? And how can you design a Zika vaccine that only induces good antibodies that protect you against Zika, but doesn't induce these other, potentially enhancing antibodies that are harmful against disease?"Dengue disease is caused by not one but four closely related types of flaviviruses, each of which can strike with a slightly different set of symptoms and severity. Getting sick with one type of dengue virus can increase the likelihood that a person will develop a second, more severe illness when infected with a separate type of dengue virus. However, after a person has been infected with two types of dengue viruses, they usually gain some degree of immune protection against future dengue disease severity.When Zika first emerged in Latin America in late 2015, many speculated whether the flavivirus, a close cousin to the dengue viruses, might interact with the dengue viruses in a similar way."The first question was, 'How will prior dengue virus infection affect Zika?' because everyone in Latin America, to some degree or another, is eventually dengue immune and has dengue antibodies," said study senior author Eva Harris, a professor of infectious diseases and vaccinology at UC Berkeley.Since 2004, Harris and her colleagues in Nicaragua have monitored a cohort of approximately 3,800 children living in Managua, the country's capital, tracking any signs of dengue disease and collecting annual blood samples to test for the virus and its antibodies. When chikungunya, another mosquito-borne virus, and Zika appeared in Nicaragua in 2014 and 2016, respectively, the cohort was expanded to capture cases of these emerging pathogens.Using data from the cohort, Harris published a 2019 study showing that prior dengue virus infection can grant a small amount of protection against Zika, and other studies now support this conclusion. But the inverse question, whether Zika antibodies protect against future dengue disease, or potentially enhance it, remained a mystery.In July 2019, Harris landed in Managua with Katzelnick, who would be stationed in Nicaragua's capital for the rest of the year as a Fogarty Global Health Fellow. The two arrived at the very beginning of what would become a massive epidemic of dengue virus Type 2, one of the more severe of the four flavors, or serotypes, of dengue, and the first major outbreak of dengue since the Zika epidemic in 2016."We watched as the epidemic spread in real time, and we started thinking, you know what, there are a lot of cases. I wonder if previous infection with Zika is pushing people into symptomatic disease?'" Harris said.The team gathered data from its pediatric cohort and from another study of children being treated at a nearby pediatric hospital. By mid-autumn, the researchers had enough evidence to prove that having a prior Zika infection made a person more likely to have a symptomatic dengue infection. And as cases mounted, they found that prior Zika infection can also enhance dengue disease severity.The team drew on the pediatric cohort's bank of blood samples going back to 2004 to investigate other patterns of disease. It found that people who had one dengue infection, followed by a Zika infection, remained at high risk of developing a second, more severe dengue infection. In addition, when a person had two sequential dengue infections, the type of dengue virus that caused the second infection impacted whether the person was protected or experienced enhanced dengue disease."I think this can really help us understand epidemics that are coming down the line," Harris said. "So, for instance, if you have a dengue Type 2 epidemic after a big Zika outbreak, you know to prepare your hospitals to treat people who might be more likely to develop a more severe disease."When we get sick, our bodies produce large proteins called antibodies to help our immune system fight the infection. These antibodies have specific chemical shapes that allow them to stick to the pathogen of concern, flagging the invader to be broken down by immune cells. For viruses like Zika and dengue, they also can coat the virus and prevent it from entering the body's cells, effectively neutralizing it.Antibody-dependent enhancement can happen when an antibody designed to stick to one virus, like Zika, tries to stick to a slightly different virus, like dengue. Antibodies to Zika virus can attach to dengue viruses, but not quite well enough to neutralize them. As a result, when a passing immune cell senses the antibody "flag" and tries to break down the dengue virus, it can actually end up getting infected by the virus."This mechanism not only allows the virus to get into more cells to infect, but also suppresses the immune response of those cells, enabling the virus to produce even more virus," Katzelnick said. "And, because they're immune cells, they are moving around the body. And so, they can initiate a larger infection."In a 2017 study, Katzelnick, Harris and the team in Nicaragua showed that infection with one dengue virus can lead to a more severe infection with a second dengue virus through antibody-dependent enhancement.Though this mechanism has complicated the search for effective vaccines for both Zika and dengue, Katzelnick and Harris say that it is still possible to design vaccines that spur the body to create antibodies that only stick to the targeted virus, and no other."Zika is still a horrible problem that has a lot of complicated ethical considerations, in part because of the way it affects pregnant women and also potentially their children," Katzelnick said. "I really hope that people keep working very hard to find ways to develop a safe vaccine, even if it's more challenging than we originally thought."
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Microbes
| 2,020 |
August 26, 2020
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https://www.sciencedaily.com/releases/2020/08/200826141353.htm
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Catching genes from chlamydiae allowed complex life to live without oxygen
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An international team of researchers has discovered a new group of Chlamydiae -- Anoxychlamydiales -- living under the ocean floor without oxygen. These Chlamydiae have genes that allow them to survive without oxygen while making hydrogen gas. The researchers found that our single-cell ancestors 'caught' these hydrogen-producing genes from ancient Chlamydiae up to two-billion years ago -- an event that was critical for the evolution of all complex life alive today. The results are published in
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Life on Earth can be classified into two main categories: eukaryotes (e.g., plants, animals, fungi, amoeba) and prokaryotes (e.g., bacteria and archaea). In comparison to relatively simple prokaryotic cells, eukaryotic cells have complex cellular organisation. How such cellular complexity evolved has puzzled scientists for decades. The prevailing hypothesis for the evolution of eukaryotes involves the merger, or symbiosis, of two prokaryotes -- an archaeon and a bacterium -- nearly two-billion years ago, in environments with little oxygen. Scientists assume that these microbes co-operated with each other to survive without oxygen by exchanging nutrients. While we do not know what these nutrient were, many scientists think that hydrogen might be the answer.To find an answer to this two-billion year old mystery, scientists look at genomes of modern prokaryotes and eukaryotes to find genes for living without oxygen and nutrient metabolism with hydrogen. Much like fossils, genomes hold clues to the evolutionary history of their ancestors. In our cells, we have a specialized factory called the mitochondrion -- or powerhouse of the cell -- that helps us make energy using the oxygen we breathe and the sugar we eat. However, some mitochondria are able to make energy without oxygen by producing hydrogen gas. Since hydrogen has been proposed to have been an important nutrient for the origin of eukaryotes, scientists think that hydrogen production was present in one of the two-billion year old partners: the archaeon or the bacterium. However, there is no evidence for this with present data.In an article published in "In our study we identified the first evidence for how eukaryotes got the genes to make hydrogen and it was from a completely unexpected source!" says co-lead author Courtney Stairs, postdoctoral researcher at Uppsala University in Sweden. Fellow co-lead author Jennah Dharamshi, PhD student from Uppsala University, adds: "We found new evidence that the eukaryotic genome has a mosaic evolutionary history, and has come not only from Archaea and the mitochondrion, but also from Chlamydiae.""Understanding where hydrogen metabolism came from in eukaryotes is important for gaining insight into how our two-billion-year old ancestors evolved," says senior author Thijs Ettema, Professor at Wageningen University and Research in The Netherlands, and coordinator of the international team of researchers. "For years, I thought that if we ever found out where eukaryotic hydrogen metabolism came from, we would have a clearer picture of how eukaryotes evolved -- however, finding out that these genes might have come from Chlamydiae has raised even more questions," Courtney Stairs adds.How did the eukaryotes get a hold of these genes?"We know that microorganisms routinely share genes with each other in a process called 'gene transfer'. We can find these transfer events by building family trees of each gene and looking for patterns in their evolution" explains Courtney Stairs. Today, the closest relatives of the archaeon that participated in the initial symbiosis are Asgard archaea. These archaea are also found at the bottom of the ocean where Anoxychlamydiales reside. "Asgard archaea and Anoxychlamydiales are both found living under the ocean floor where there is no oxygen" Thijs Ettema explains, "their cohabitation could have allowed for genes to be transferred between the ancestors of these microbes."Finding chlamydiae that can live without oxygen has important implications in itself. These bacteria are typically known as pathogens of humans and other animals, even though they can also infect single-cell eukaryotes such as amoeba. All chlamydiae known to date live inside eukaryotic cells."Finding chlamydiae that might be able to live without oxygen, produce hydrogen, and live outside a eukaryote challenges our previously held conceptions" says Jennah Dharamshi, "our findings suggest that chlamydiae may be important members of the ecosystem on the ocean floor and that perhaps all chlamydiae are not that bad after all."
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Microbes
| 2,020 |
August 25, 2020
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https://www.sciencedaily.com/releases/2020/08/200825110729.htm
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The secret life of melons revealed: 'Jumping sequences' may alter gene expression
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On the surface, the humble melon may just look like a tasty treat to most. But researchers from Japan have found that this fruit has hidden depths: retrotransposons (sometimes called "jumping sequences") may change how genes are expressed.
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In a study published recently in Melons comprise one of the most economically important fruit crops globally. A special feature of melons is the coexistence of two fruit types: climacteric (which produce ethylene and exhibit a burst in cellular respiration as ripening begins), and non-climacteric. Ethylene is a plant hormone important to the regulation of climacteric fruit-ripening traits such as shelf life, which is of major economic importance."Because Harukei-3 melons produce ethylene during ripening, we wanted to look at ethylene-related gene expression in this type of melon," says lead author of the study Professor Hiroshi Ezura. "Harukei-3 produces an especially sweet fruit if grown in the right seasons. Because of its taste and attractive appearance, Harukei-3 has been used for a long time in Japan as a standard type for breeding high-grade muskmelon."To examine ethylene-related gene expression, the researchers assembled the whole genome sequence of Harukei-3 by using third-generation nanopore sequencing paired with optical mapping and next-generation sequencing."We compared the genome of Harukei-3 with other melon genomes. Interestingly, we found that there are genome-wide presence/absence polymorphisms of retrotransposon-related sequences between melon accessions, and 160 (39%) were transcriptionally induced in post-harvest ripening fruit samples. They were also co-expressed with neighboring genes," explains Dr. Ryoichi Yano, senior author. "We also found that some retrotransposon-related sequences were transcribed when the plants were subjected to heat stress."Retrotransposons are transposons (also referred to as "jumping sequences" because they can change their positions within a genome) with sequences similar to those of retroviruses."Our findings suggest that retrotransposons contributed to changes in gene expression patterns when melon genomes were diversifying. Retrotransposons may also affect gene expression that brings on fruit ripening," says Professor Ezura.The Harukei-3 genome assembly, together with other data generated in this study, is available in the Melonet-DB database. Combined with future updates, this database will contribute to the functional genomic study of melons, especially reverse genetics using genome editing.
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Microbes
| 2,020 |
August 25, 2020
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https://www.sciencedaily.com/releases/2020/08/200825110546.htm
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Treating COVID-19 could lead to increased antimicrobial resistance
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The use of antibiotics in people with COVID-19 could result in increased resistance to the drugs' benefits among the wider population, a new study suggests.
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Patients hospitalised as a result of the virus are being given a combination of medications to prevent possible secondary bacterial infections.However, research by the University of Plymouth and Royal Cornwall Hospital Trust suggests their increased use during the pandemic could be placing an additional burden on waste water treatment works.Writing in the This would be particularly acute in receiving waters from waste water treatment works serving large hospitals, or emergency 'Nightingale' hospitals, where there is a concentration of COVID-19 patients.The findings are based on reports that up to 95% of COVID-19 inpatients are being prescribed antibiotics as part of their treatment, and concerns that such a large-scale drug administration could have wider environmental implications.Sean Comber, Professor of Environmental Chemistry in Plymouth and the article's lead author, said: "COVID-19 has had an impact on almost every aspect of our lives. But this study shows its legacy could be felt long after the current pandemic has been brought under control. From our previous research, we know that significant quantities of commonly prescribed drugs do pass through treatment works and into our water courses. By developing a greater understanding of their effects, we can potentially inform future decisions on prescribing during pandemics, but also on the location of emergency hospitals and wider drug and waste management."The COVID-19 guidance issued by the National Institute for Health and Care Excellence (NICE) suggests patients with COVID-19 should be treated with doxycycline and either amoxicillin or a combination of other medications if a bacterial infection is suspected, but to withhold or stop antibiotics if a bacterial infection is unlikely.Neil Powell, Consultant Pharmacist at the Royal Cornwall Hospital said: "Common with other hospitalised patients in the UK, and other countries, the majority of our patients with COVID symptoms were prescribed antibiotics because it is very difficult to know whether a patient presenting with symptoms of COVID has an overlying bacterial infection or not. We did a lot of work to try and identify those patients who were unlikely to have a bacterial infection complicating their viral COVID infections in an attempt to reduce the amount of antibiotic exposure to our patients and consequently the environment."This research combined patient numbers for UK emergency hospitals set up temporarily around the country with waste water treatment work capacity and available river water dilution serving the emergency hospital and associated town.Using available environmental impact data and modelling tools developed by the UK water industry, it focussed on one UK emergency hospital -- Harrogate, geared up to treat around 500 people -- and showed the risks posed by doxycycline was low, assuming the hospital was at full capacity.Tom Hutchinson, Professor of Environment and Health at the University and a co-author on the research, added: "This is a comprehensive environmental safety assessment which addresses potential risks to fish populations and the food webs they depend on. The data for amoxicillin indicated that while there was little threat of direct impacts on fish populations and other wildlife, there is a potential environmental concern for selection of AMR if at 100% capacity."Amoxicillin is used to treat everything from pneumonia and throat infections to skin and ear infections.Mathew Upton, Professor of Medical Microbiology at the University and a co-author on the research, added: "Antibiotics underpin all of modern medicine, but AMR is an issue that could impact millions of lives in the decades to come. Currently, the COVID-19 pandemic is causing immense suffering and loss of life across the globe, but AMR has been -- and will remain -- one of the most significant threats to global human health. We conducted this study so that we can begin to understand the wider impact of global pandemics on human health. It is clear that mass prescribing of antibiotics will lead to increased levels in the environment and we know this can select for resistant bacteria. Studies like this are essential so that we can plan how to guide antibiotic prescription in future pandemics."
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Microbes
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August 24, 2020
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https://www.sciencedaily.com/releases/2020/08/200824131805.htm
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Are antivitamins the new antibiotics?
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Antibiotics are among the most important discoveries of modern medicine and have saved millions of lives since the discovery of penicillin almost 100 years ago. Many diseases caused by bacterial infections -- such as pneumonia, meningitis or septicaemia -- are successfully treated with antibiotics. However, bacteria can develop resistance to antibiotics which then leaves doctors struggling to find effective treatments. Particularly problematic are pathogens which develop multi-drug resistance and are unaffected by most antibiotics. This leads to severe disease progression in affected patients, often with a fatal outcome. Scientists all over the world are therefore engaged in the search for new antibiotics. Researchers at the University of Göttingen and the Max Planck Institute for Biophysical Chemistry Göttingen have now described a promising new approach involving "antivitamins" to develop new classes of antibiotics. The results were published in the journal
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Antivitamins are substances that inhibit the biological function of a genuine vitamin. Some antivitamins have a similar chemical structure to those of the actual vitamin whose action they block or restrict. For this study, Professor Kai Tittmann's team from the Göttingen Center for Molecular Biosciences at the University of Göttingen worked together with Professor Bert de Groot's group from the Max Planck Institute for Biophysical Chemistry Göttingen and Professor Tadgh Begley from Texas A&M University (USA). Together they investigated the mechanism of action at the atomic level of a naturally occurring antivitamin of vitamin B1. Some bacteria are able to produce a toxic form of this vital vitamin B1 to kill competing bacteria. This particular antivitamin has only a single atom in addition to the natural vitamin in a seemingly unimportant place and the exciting research question was why the action of the vitamin was still prevented or "poisoned."Tittmann's team used high-resolution protein crystallography to investigate how the antivitamin inhibits an important protein from the central metabolism of bacteria. The researchers found that the "dance of the protons," which can normally be observed in functioning proteins, almost completely ceases to function and the protein no longer works. "Just one extra atom in the antivitamin acts like a grain of sand in a complex gear system by blocking its finely tuned mechanics," explains Tittmann. It is interesting to note that human proteins are able to cope relatively well with the antivitamin and continue working. The chemist de Groot and his team used computer simulations to find out why this is so. "The human proteins either do not bind to the antivitamin at all or in such a way that they are not 'poisoned'," says the Max Planck researcher. The difference between the effects of the antivitamin on bacteria and on human proteins opens up the possibility of using it as an antibiotic in the future and thus creating new therapeutic alternatives.The research project was funded by the German Research Foundation (DFG).
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Microbes
| 2,020 |
August 24, 2020
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https://www.sciencedaily.com/releases/2020/08/200824131803.htm
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Each human gut has a viral 'fingerprint'
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Each person's gut virus composition is as unique as a fingerprint, according to the first study to assemble a comprehensive database of viral populations in the human digestive system.
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An analysis of viruses in the guts of healthy Westerners also showed that dips and peaks in the diversity of virus types between childhood and old age mirror bacterial changes over the course of the lifespan.The Gut Virome Database developed by Ohio State University scientists identifies 33,242 unique viral populations that are present in the human gut. (A collection of viruses like those in the human gut is called a virome.) This is not cause for alarm: Most viruses don't cause disease.In fact, the more scientists learn about viruses, the more they see them as part of the human ecosystem -- suggesting viruses have potential to represent a new class of drugs that could fight disease-causing bacteria, especially those resistant to antibiotics. Better knowledge of viruses in the gut environment could even improve understanding of the gastrointestinal symptoms experienced by some of the sickest COVID-19 patients.The researchers plan to update the open-access database on a regular basis."We've established a robust starting point to see what the virome looks like in humans," said study co-author Olivier Zablocki, a postdoctoral researcher in microbiology at Ohio State. "If we can characterize the viruses that are keeping us healthy, we might be able to harness that information to design future therapeutics for pathogens that can't otherwise be treated with drugs."The study is published today (Aug. 24) in the journal Talk of the good and bad bacteria in the gut microbiome is commonplace these days, but viruses in the gut -- and everywhere -- are hard to detect because their genomes don't contain a common signature gene sequence that bacteria genomes do. So much of the vast sequence space of viruses remains unexplored that it is often referred to as "dark matter."For this work, the researchers started with data from 32 studies over about a decade that had looked at gut viruses in a total of 1,986 healthy and sick people in 16 countries. Using techniques to detect virus genomes, the team identified more than 33,000 different viral populations."We used machine learning on known viruses to help us identify the unknown viruses," said first author Ann Gregory, who completed this work while she was a graduate student at Ohio State. "We were interested in how many types of viruses we could see in the gut, and we determined that by how many types of genomes we could see since we couldn't visually see the viruses."Their analysis confirmed findings from smaller studies suggesting that though a few viral populations were shared within a subset of people, there is no core group of gut viruses common to all humans.A few trends were identified, however. In healthy Western individuals, age influences the diversity of viruses in the gut, which increases significantly from childhood to adulthood, and then decreases after age 65. The pattern matches what is known about ebbs and flows of gut bacterial diversity with one exception: Infant guts with underdeveloped immune systems are teeming with a range of virus types, but few bacteria varieties.People living in non-Western countries had higher gut virus diversity than Westerners. Gregory said other research has shown that non-Western individuals who move to the United States or another Western country lose that microbiome diversity, suggesting diet and environment drive virome differences. (For example, the scientists found some intact plant viruses in the gut -- the only way for them to get there is through the diet.) Variations in viral diversity could also be seen in healthy versus sick participants in the 32 studies analyzed."A general rule of thumb for ecology is that higher diversity leads to a healthier ecosystem," Gregory said. "We know that more diversity of viruses and microbes is usually associated with a healthier individual. And we saw that healthier individuals tend to have a higher diversity of viruses, indicating that these viruses may be potentially doing something positive and having a beneficial role."Almost all of the populations -- 97.7 percent -- were phages, which are viruses that infect bacteria. Viruses have no function without a host -- they drift in an environment until they infect another organism, taking advantage of its properties to make copies of themselves. The most-studied viruses kill their host cells, but scientists in the Ohio State lab in which Gregory and Zablocki worked have discovered more and more phage-type viruses that coexist with their host microbes and even produce genes that help the host cells compete and survive.The leader of that lab, senior study author Matthew Sullivan, has his sights set on "phage therapy" -- the 100-year-old idea of using phages to kill antibiotic-resistant pathogens or superbugs."Phages are part of a vast interconnected network of organisms that live with us and on us, and when broad-spectrum antibiotics are used to fight against infection, they also harm our natural microbiome," Sullivan said. "We are building out a toolkit to scale our understanding and capabilities to use phages to tune disturbed microbiomes back toward a healthy state."Importantly, such a therapeutic should impact not only our human microbiome, but also that in other animals, plants and engineered systems to fight pathogens and superbugs. They could also provide a foundation for something we might have to consider in the world's oceans to combat climate change."A professor of microbiology and civil, environmental and geodetic engineering, Sullivan has helped establish cross-disciplinary research collaborations at Ohio State. He recently founded and directs Ohio State's new Center of Microbiome Science and co-directs the Infectious Diseases Institute's Microbial Communities program.Zablocki noted that there is still a lot to learn about the functions of viruses in the gut -- both beneficial and harmful."I see it as the chicken and the egg," he said. "We see the disease and we see the community structure. Was it because of this community structure that the disease occurred, or is the disease causing the community structure that we see? This standardized dataset will enable us to pursue those questions."This work was supported by the Ohio Supercomputer Center and funded by the Gordon and Betty Moore Foundation, the National Institutes of Health and Ohio State's Center of Microbiome Science.
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Microbes
| 2,020 |
August 24, 2020
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https://www.sciencedaily.com/releases/2020/08/200824105926.htm
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Frequent use of antimicrobial drugs in early life shifts bacterial profiles in saliva
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The human microbiota plays an important role in health and well-being by assisting in digestion, producing nutrients, resisting invading pathogens and regulating metabolism and the immune system.
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We use antimicrobial (AM) drugs to treat common infections even though they have an immediate effect on microbial diversity and composition.Most of the studies have earlier focused on faecal (gut) microbiota, but microbes in other niches of the body have also showed importance for human health and well-being.The Finnish Health in Teens study (Fin-HIT) is a cohort study including over 11,000 Finnish adolescents. In the most recent Fin-HIT study researchers tried to find the associations of lifelong AMs use with saliva microbiota diversity and composition in preadolescents. They used data from 808 randomly selected children in the Fin-HIT cohort with objective register data on AM purchases from the Social Insurance Institution of Finland (KELA).On average, the children had 7.4 AM purchases during their lifespan until on average 12 years. The four most commonly used AMs were amoxicillin (43.7 %), azithromycin (24.9 %), amoxicillin-clavulanate (18.7 %) and phenoxymethylpenicillin (6.8 %).Researchers showed in the study that frequent use of antimicrobial drugs shifted bacterial profiles in saliva. The frequent use of any AMs affected saliva microbiota."Microbial composition differed between high, medium and low users of AMs. These effects are also gender- and AM-dependent," says Sajan Raju, Post Doctoral Researcher at University of Helsinki.Azithromycin is used for example to middle ear infections, strep throat and pneumonia. According to the study, azithromycin had the strongest associations to shifts in bacterial profiles: each course decreased the microbiota diversity. This was more strongly observed in girls than in boys."Our findings emphasize a concern for high azithromycin use, which substantially impaired the bacterial diversity and affected composition as well," says Raju.In boys, amoxicillin affected the microbial composition more than in girls. As well as azithromycin, amoxicillin is also widely used to middle ear infections and strep throat. The use of amoxicillin and amoxicillin-clavulanate was associated with the largest decrease in abundance of Rikenellaceae family.AM use in general was associated with a decrease of Paludibacter and pathways related to amino acid degradations.Unforeseen health impacts in the future?The contribution of lifelong AM use on saliva microbiota is unknown and AM use might have unforeseen health impacts in the future."It can have health impacts such as inducing obesity or antibiotic resistant bacteria," says Raju.The majority of children (85 %) in the study were exposed to AMs during the first three years of life.In the study the researchers could not confirm that the purchased AMs were taken. Neither the dental status of the adolescents was not assessed in the study.
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Microbes
| 2,020 |
August 24, 2020
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https://www.sciencedaily.com/releases/2020/08/200824105602.htm
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Less flocking behavior among microorganisms reduces the risk of being eaten
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When algae and bacteria with different swimming gaits gather in large groups, their flocking behaviour diminishes, something that may reduce the risk of falling victim to aquatic predators. This finding is presented in an international study led from Lund University in Sweden.
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Flocking behaviour arises seemingly spontaneously in a group of independent individuals without a clear leader. This behaviour occurs among many types of organisms, from bacteria to mammals and humans. In a new study published in "We have looked at a mixture of two types of swimmers. Those that use 'breaststroke', namely certain types of algae, and those that swim with a 'propeller' behind them, like most bacteria," says Joakim Stenhammar, chemistry researcher at Lund University.Previous research has shown that microorganisms with the same swimming technique can sense, and are affected by, each other's fluid flows. This means they can move in a synchronised way over long length scales several times faster than an individual bacterium can swim.However, in the new study the Lund researchers could establish through using computer simulations and theoretical models that this flocking behaviour completely disappears when microorganisms with different swimming styles are mixed."Their collective fluid flows then behave as though the individuals could not sense each other's presence. You could say that the microorganisms gain a cloak of invisibility," says Joakim Stenhammar.The new study is an important piece of the puzzle in understanding how flocking behaviour works in biological systems. Now the work will continue with the study of increasingly detailed models of how actual microorganisms behave. This will enable comparisons between the theoretical results and experimental observations."On a biological level there may be advantages from symbiotic ecosystems in which bacteria and algae live together. The suppression of flocking behaviour may reduce the risk of being eaten, as many aquatic predators sense the fluid flows to localise prey," concludes Joakim Stenhammar.
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Microbes
| 2,020 |
August 20, 2020
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https://www.sciencedaily.com/releases/2020/08/200820143237.htm
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Vaccine that harnesses antifungal immunity protects mice from staph infection
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Immunization of mice with a new vaccine consisting of fungal particles loaded with
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The researchers developed a new vaccine called 4X-SA-GP, which consists of fungal ?-glucan particles loaded with four The authors conclude, "We need some creative new approaches to explore towards developing a
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Microbes
| 2,020 |
August 19, 2020
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https://www.sciencedaily.com/releases/2020/08/200819110915.htm
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Bacteria can defuse dangerous chemical in Passaic River
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Bacteria that can help defuse highly toxic dioxin in sediments in the Passaic River -- a Superfund hazardous waste site -- could eventually aid cleanup efforts at other dioxin-contaminated sites around the world, according to Rutgers scientists.
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Their research, published in the journal "The bacteria-driven process we observed greatly decreases the toxicity of dioxin," said senior author Donna E. Fennell, a professor who chairs the Department of Environmental Sciences in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick."Our results showed that although the process is quite slow, it can be enhanced and may even have the potential to remove all toxic chlorines from the compound," said lead author Rachel K. Dean, a Rutgers doctoral student.In a process known as dechlorination, the bacteria remove chlorine atoms from 2,3,7,8-Tetrachlorodibenzo?These chemicals can cause cancer, reproductive and developmental problems and immune system damage, according to the U.S. Environmental Protection Agency. They also can interfere with hormones in the body.In New Jersey, the decades-old Diamond Alkali Superfund site includes a former chemical manufacturing facility in Newark, a 17-mile tidal stretch of the Passaic River and tributaries, Newark Bay and portions of the Hackensack River, Arthur Kill and Kill van Kull, according to the EPA.The 2,3,7,8-TeCDD dioxin is a byproduct of combustion and chemical product manufacturing, including the herbicides in Agent Orange. Sampling revealed high levels of dioxin in 1983 and the site landed on the Superfund National Priorities List a year later. Dioxin, polychlorinated biphenyls, metals, polycyclic aromatic hydrocarbons and pesticides were found in sediment in the Lower Passaic River.Though dredging is required to remove the most highly contaminated sediments in the Passaic River, some contamination has spread and will remain in the river and estuary, where it could be transformed by the bacteria over time, according to the Rutgers scientists.In the study, scientists took solid material from the river bottom and mixed it with water and other nutrients in the lab to make mud in bottles. Then they added 2,3,7,8-TeCDD and another chemical (dichlorobenzene) that boosted dechlorination by bacteria.The Rutgers scientists revealed bacteria that are likely involved in the dechlorination process -- a novelThe next goal is to try to identify the enzymes involved in dechlorination so cleanup technologies could be developed that lead to more dechlorination at this and other contaminated sites, the study says.Rutgers co-authors include Cassidy R. Schneider, who earned bachelor's and master's degrees at Rutgers; Haider S. Almnehlawi, who is earning a doctorate at Rutgers and is a faculty member at Al-Muthanna University; and Professor Katherine S. Dawson, an assistant professor in the Rutgers Department of Environmental Sciences.
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Microbes
| 2,020 |
August 18, 2020
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https://www.sciencedaily.com/releases/2020/08/200818103841.htm
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Insect wings inspire new ways to fight superbugs
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Scientists have revealed how nanomaterials inspired by insect wings are able to destroy bacteria on contact.
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The wings of cicadas and dragonflies are natural bacteria killers, a phenomenon that has spurred researchers searching for ways to defeat drug-resistant superbugs.New anti-bacterial surfaces are being developed, featuring different nanopatterns that mimic the deadly action of insect wings, but scientists are only beginning to unravel the mysteries of how they work.In a review published in Lead author, RMIT University's Distinguished Professor Elena Ivanova, said finding non-chemical ways of killing bacteria was critical, with more than 700,000 people dying each year due to drug-resistant bacterial infection."Bacterial resistance to antibiotics is one of the greatest threats to global health and routine treatment of infection is becoming increasingly difficult," Ivanova said."When we look to nature for ideas, we find insects have evolved highly effective anti-bacterial systems."If we can understand exactly how insect-inspired nanopatterns kill bacteria, we can be more precise in engineering these shapes to improve their effectiveness against infections."Our ultimate goal is to develop low-cost and scaleable anti-bacterial surfaces for use in implants and in hospitals, to deliver powerful new weapons in the fight against deadly superbugs."The wings of cicadas and dragonflies are covered in tiny nanopillars, which were the first nanopatterns developed by scientists aiming to imitate their bactericidal effects.Since then, they've also precisely engineered other nanoshapes like sheets and wires, all designed to physically damage bacteria cells.Bacteria that land on these nanostructures find themselves pulled, stretched or sliced apart, rupturing the bacterial cell membrane and eventually killing them.The new review for the first time categorises the different ways these surface nanopatterns deliver the necessary mechanical forces to burst the cell membrane."Our synthetic biomimetic nanostructures vary substantially in their anti-bacterial performance and it's not always clear why," Ivanova said."We have also struggled to work out the optimal shape and dimensions of a particular nanopattern, to maximise its lethal power."While the synthetic surfaces we've been developing take nature to the next level, even looking at dragonflies, for example, we see that different species have wings that are better at killing some bacteria than others."When we examine the wings at the nanoscale, we see differences in the density, height and diameter of the nanopillars that cover the surfaces of these wings, so we know that getting the nanostructures right is key."Ivanova said producing nanostructured surfaces in large volumes cost-effectively, so they could be used in medical or industrial applications, remained a challenge.But recent advancements in nanofabrication technologies have shown promise for opening a new era of biomedical antimicrobial nanotechnology, she said.Video:
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Microbes
| 2,020 |
August 18, 2020
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https://www.sciencedaily.com/releases/2020/08/200818094059.htm
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Escape artists: How vibrio bacteria break out of cells
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As soon as the foodborne pathogen
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Now, UT Southwestern scientists have discovered the surprising route that "The more we understand how bacteria are manipulating host cells at a molecular level, the more we understand how they cause disease," says study leader Kim Orth, Ph.D., professor of molecular biology and biochemistry at UTSW and a Howard Hughes Medical Institute investigator. "Bacteria have many different mechanisms to escape, but this stood out because it's an especially novel one."Vibrio bacteria are found in warm seawater and humans become infected by eating raw shellfish such as oysters. About a dozen different species of Vibrio can cause human illness; About a decade ago, Orth's group first revealed how "We started to get a good understanding of how this pathogen gets inside cells and maintains an existence," says Orth. "We assumed that it was also using components of the T3SS2 to get out of cells again."But when Orth and her colleagues started studying the egress of Orth's team identified a lipase known as VPA0226 and thought they'd found their answer, assuming the lipase digested the membranes of human cells. But they were in for another surprise. When they tracked the activity of the lipase, they discovered that it instead headed for the mitochondria of cells, where it modified membrane cholesterol molecules. Over seven to eight hours, as these cholesterol molecules are modified, the cell membrane becomes weak. By this time, "This is the only report we know of where a bacterium uses this kind of T2SS lipase to egress from a host cell that was invaded in a T3SS2 dependent way," says Suneeta Chimalapati, Ph.D., a research scientist in the Orth lab and co-first author of the study.To confirm the role of VPA0226, de Souza Santos and Chimalapati tested what happened when The new observation likely won't have any immediate therapeutic implications, the researchers say; "We really had tunnel vision thinking the T3SS2 dominated everything Vibrio did, but this shows how many other tools it has on hand to use for its pathogenesis," says Orth, who holds the Earl A. Forsythe Chair in Biomedical Science and is a W.W. Caruth, Jr. Scholar in Biomedical Research. She was recently elected to the National Academy of Sciences.Other UTSW researchers who contributed to this study were Alexander Lafrance, Ann Ray, Wan-Ru Lee, Giomar Rivera-Cancel, Goncalo Vale, Krzysztof Pawlowski, Matthew Mitsche, Jeffrey McDonald, and Jen Liou.This research was supported by funds from the Howard Hughes Medical Institute, the National Institutes of Health (R01 GM115188, RO1 GM113079, PO1 HL20948), the Once Upon a Time Foundation, and The Welch Foundation (I-1561).
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Microbes
| 2,020 |
August 18, 2020
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https://www.sciencedaily.com/releases/2020/08/200818094026.htm
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Airborne viruses can spread on dust, non-respiratory particles
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Influenza viruses can spread through the air on dust, fibers and other microscopic particles, according to new research from the University of California, Davis and the Icahn School of Medicine at Mt. Sinai. The findings, with obvious implications for coronavirus transmission as well as influenza, are published Aug. 18 in
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"It's really shocking to most virologists and epidemiologists that airborne dust, rather than expiratory droplets, can carry influenza virus capable of infecting animals," said Professor William Ristenpart of the UC Davis Department of Chemical Engineering, who helped lead the research. "The implicit assumption is always that airborne transmission occurs because of respiratory droplets emitted by coughing, sneezing, or talking. Transmission via dust opens up whole new areas of investigation and has profound implications for how we interpret laboratory experiments as well as epidemiological investigations of outbreaks."Influenza virus is thought to spread by several different routes, including in droplets exhaled from the respiratory tract or on secondary objects such as door handles or used tissues. These secondary objects are called fomites. Yet little is known about which routes are the most important. The answer may be different for different strains of influenza virus or for other respiratory viruses, including coronaviruses such as SARS-CoV2.In the new study, UC Davis engineering graduate student Sima Asadi and Ristenpart teamed up with virologists led by Dr. Nicole Bouvier at Mt. Sinai to look at whether tiny, non-respiratory particles they call "aerosolized fomites" could carry influenza virus between guinea pigs.Using an automated particle sizer to count airborne particles, they found that uninfected guinea pigs give off spikes of up to 1,000 particles per second as they move around the cage. Particles given off by the animals' breathing were at a constant, much lower rate.Immune guinea pigs with influenza virus painted on their fur could transmit the virus through the air to other, susceptible guinea pigs, showing that the virus did not have to come directly from the respiratory tract to be infectious.Finally, the researchers tested whether microscopic fibers from an inanimate object could carry infectious viruses. They treated paper facial tissues with influenza virus, let them dry out, then crumpled them in front of the automated particle sizer. Crumpling the tissues released up to 900 particles per second in a size range that could be inhaled, they found. They were also able to infect cells from these particles released from the virus-contaminated paper tissues.The work was supported by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
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Microbes
| 2,020 |
August 17, 2020
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https://www.sciencedaily.com/releases/2020/08/200817123110.htm
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Designed bacteria produce coral-antibiotic against multi-resistant TB
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Thomas Brück saw the sea whip Antillogorgia elisabethae for the first time 17 years ago while diving on a research trip to the Bahamas. He still remembers this encounter vividly, which took place 18 meters below the water's surface: "Their polyp-covered, violet branchlets moved gently in the current. A fascinating living organism!" As it also contains various biologically active compounds, the biochemist since then has studied the natural product biosynthesis of this soft coral.
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Sea whips are protected; despite this, their existence is in danger. The collection and sale of dried corals is a lucrative business, as these contain various active agents, including an anti-inflammatory molecule called pseudopterosin, which is used in the cosmetics industry for years."Coral reefs fix and store the greenhouse gas carbon dioxide and are biodiversity hotspots. If we want to protect the world's reefs, we have to generate such biologically active natural products, via sustainable processes," says Brück.Together with his team at the Werner Siemens Chair of Synthetic Biotechnology, he has now managed for the first time to produce one of the sea whip's active agents in the laboratory -- without the need for a single reef inhabitant. The molecule "erogorgiaene" is an antibiotic. Initial bioactivity tests show, that it is suitable for fighting multi-resistant tuberculosis pathogens.Previously, a use of the active agent was almost unthinkable: The sea whip contains only extremely small quantities of erogorgiaene and is additionally protected -- using it as a raw material source would be neither financially feasible nor ecologically responsible. Although production via conventional chemical synthesis is possible, it is complex and associated with toxic waste. A kilo of the active agent would cost around EUR 21,000."However, with biotechnological methods, a consolidated erogorgiaene production is feasible, in a more environmentally friendly manner and much cheaper. With this method, the production costs per kilo would only be around EUR 9,000," emphasizes Brück.The new method, which he has developed together with colleagues from Berlin, Canada, and Australia, consists of only two steps: The main work is done by genetically optimized bacteria that feed on glycerin -- a residual substance from biodiesel production.The bacteria generate a molecule, that can then be converted into the desired active agent using a highly selective enzymatic step. No waste is produced in the process, as all ancillary products can be reused in a circular manner. A patent has been filed for the innovative production method."The new technology platform for the production of bioactive natural products via biotechnological methodologies complies with all 12 criteria of The research team is now working on the biotechnological production of another coral active agent: Using nature as a model, the molecule erogorgiaene is to be converted into the active agent pseudopteropsin in the laboratory.Medical professionals are placing great hope on the latter: Clinical studies have shown that pseudopteropsin inhibits inflammations thanks to a new mechanism of action. Thus, it is a potential therapeutic candidate to control excessive inflammatory reactions, for example in the case of viral infections, such as Covid-19, or during age-related chronic inflammations.
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Microbes
| 2,020 |
August 17, 2020
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https://www.sciencedaily.com/releases/2020/08/200817123109.htm
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Survival of the fit-ish
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It can be hard to dispute the common adage 'survival of the fittest'. After all, "most of the genes in the genome are there because they're doing something good," says Sarah Zanders, PhD, assistant investigator at the Stowers Institute for Medical Research. But, she says, "others are just there because they've figured out a way to be there."
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The conventional understanding of evolution is that genes encoding a beneficial function are the most frequently transmitted, which ensures that the fittest organisms -- the ones that have traits most favorable for their environment -- survive. Less known is the fact that there exist parasitic gene elements within an organism that are doing just the opposite."The way one could think of it is that the genome is like a society," explains Zanders. "Within that society, there are individuals who derive their living from doing good things and making valuable contributions. But there are others who don't contribute in beneficial ways and are actually harmful to society," explains Zanders.The Zanders Lab studies parasitic genes in Meiosis is the process of cell division through which sexually-reproducing organisms form gametes -- such as egg and sperm cells in humans, or spores in yeast -- to propagate the next generation. Normally, this process results in gametes that inherit one of two copies of each chromosome carried by the parent cell, and each copy is transmitted to gametes at an equal rate. Meiotic drivers, however, short-circuit this law of Mendelian segregation."Usually all the alleles -- or variants of a particular gene -- get a fair chance, and natural selection can pick the best ones," explains Zanders. "But alleles that are meiotic drivers select themselves even if they're not the best option. And they're never the best option."In a paper published online August 13, 2020, in Usually, to propagate laboratory strains of "Outcrossing can have many advantages," says Bravo Núñez, such as providing a normal allele of a gene to rescue the effect of a mutant allele. "But the meiotic drive genes that we study actually exert their deleterious effect in the heterozygous scenario, where the alleles of a gene are not the same."One illuminating experiment they did was to compare outcomes of inbred and outcrossed "Rec12 usually promotes fertility," says Bravo Núñez. "When we removed "When you have heterozygosity of "We think of "Having that extra chromosome is not good, and the yeast colonies look unusual, small, and irregular. But after they continue to grow for a while, the cells lose that extra chromosome and then they can thrive as haploids. So, this step is actually just temporary," says Bravo Núñez.Precisely because meiotic drivers exert their influence in a heterozygous scenario, they are easy to miss. "There are many flavors of meiotic drive. Some forms of meiotic drive are hard to measure experimentally because the bias is so subtle," says Zanders. "We're not the first to study meiotic drivers in depth. We just have a better model system now, so we can make more progress faster.""Drive systems tend to be repetitive, and you can usually find them in various copies in genomes," says Bravo Núñez. "They have, in many cases, already been found in other systems, such as fungi, mice, and fruit flies, but are not yet fully characterized." The study of meiotic drivers in "Humans certainly have meiotic drive genes. Whether or not they have meiotic drive genes of the gamete-killing type is unclear," says Zanders. "Meiotic drive has likely affected the evolution of human centromeres, which are regions of chromosomes that are very important for proper chromosome segregation. Certain chromosome fusions exhibit meiotic drive in humans, as do sequences that are involved in DNA recombination. We're going to continue focusing on these and other parasitic gene elements, their strategies, and their effects."Other coauthors of this work include Ibrahim M. Sabbarini and Lauren E. Eide from the Stowers Institute and Robert L. Unckless, PhD, from the University of Kansas.
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Microbes
| 2,020 |
August 17, 2020
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https://www.sciencedaily.com/releases/2020/08/200817104311.htm
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Stopping tooth decay before it starts -- without killing bacteria
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Oral bacteria are ready to spring into action the moment a dental hygienist finishes scraping plaque off a patient's teeth. Eating sugar or other carbohydrates causes the bacteria to quickly rebuild this tough and sticky biofilm and to produce acids that corrode tooth enamel, leading to cavities. Scientists now report a treatment that could someday stop plaque and cavities from forming in the first place, using a new type of cerium nanoparticle formulation that would be applied to teeth at the dentist's office.
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The researchers will present their progress toward this goal today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. The mouth contains more than 700 species of bacteria, says Russell Pesavento, D.D.S., Ph.D., the project's principal investigator. They include beneficial bacteria that help digest food or keep other microbes in check. They also include harmful streptococcal species, including Dentists and consumers can fight back with products including stannous fluoride to inhibit plaque, and silver nitrate or silver diamine fluoride to stop existing tooth decay. Researchers have also studied nanoparticles made of zinc oxide, copper oxide or silver to treat dental infections. Although bactericidal agents such as these have their place in dentistry, repeated applications could lead to both stained teeth and bacterial resistance, according to Pesavento, who is at the University of Illinois at Chicago. "Also, these agents are not selective, so they kill many types of bacteria in your mouth, even good ones," he explains.So, Pesavento wanted to find an alternative that wouldn't indiscriminately kill bacteria in the mouth and that would help prevent tooth decay, rather than treat cavities after the fact. He and his research group turned to cerium oxide nanoparticles. Other teams had examined the effects of various types of cerium oxide nanoparticles on microbes, though only a few had looked at their effects on clinically relevant bacteria under initial biofilm formation conditions. Those that did so prepared their nanoparticles via oxidation-reduction reactions or pH-driven precipitation reactions, or bought nanoparticles from commercial sources. Those prior formulations either had no effect or even promoted biofilm growth in lab tests, he says.But Pesavento persevered because the properties and behavior of nanoparticles depend, at least partially, on how they're prepared. His team produced their nanoparticles by dissolving ceric ammonium nitrate or sulfate salts in water. Other researchers had previously made the particles this way but hadn't tested their effects on biofilms. When the researchers seeded polystyrene plates with "The advantage of our treatment is that it looks to be less harmful to oral bacteria, in many cases not killing them," Pesavento says. Instead, the nanoparticles merely prevented microbes from sticking to polystyrene surfaces and forming adherent biofilms. In addition, the nanoparticles' toxicity and metabolic effects in human oral cells in petri dishes were less than those of silver nitrate.Pesavento, who was awarded a patent in July, would like to combine the nanoparticles with enamel-strengthening fluoride in a formulation that dentists could paint on a patient's teeth. But, he notes, much work must be done before that concept can be realized. For now, the team is experimenting with coatings to stabilize the nanoparticles at a neutral or slightly basic pH -- closer to the pH of saliva and healthier for teeth than the present acidic solution. His team has also begun working with bacteria linked to the development of gingivitis and has found one particular coated nanoparticle that outcompeted stannous fluoride in limiting the formation of adherent biofilms under similar conditions. Pesavento and his team will continue to test the treatment in the presence of other bacterial strains typically present in the mouth, as well as test its effects on human cells of the lower digestive tract to gain a better sense of overall safety for patients.
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Microbes
| 2,020 |
August 17, 2020
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https://www.sciencedaily.com/releases/2020/08/200817104253.htm
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Realtime observation of structural dynamic of influenza A hemagglutinin during viral entry
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Unlike living organisms, to avoid extinction, viruses need to hijack living host machineries to generate new viruses. The devastating respiratory virus, influenza A virus, utilize its hemagglutinin (HA) proteins to search for suitable host cells. Generally, HA has two important functions: selection of host cell and viral entry. Upon attaching to host cells, Influenza A virus are brought into host cells via endocytosis. A lipid bilayer cargo, known as endosome, carries influenza A virus from cell membrane into cytoplasm of host cell. Although the environment inside endosome is acidic, influenza A virus remains alive. More strikingly, HA undergoes structural change to mediate viral membrane to fuse with host endosomal membrane to form a hole in order to release viral components. Generation of this fusion event is elaborated as fusogenic, and hence structural changes of HA needed for this event is called as fusogenic transition. The mechanism of this event has been kept in Pandora's Box for decades despite extensive studies have been done to reveal its mystery. Now, Keesiang Lim and Richard Wong from Kanazawa University and colleagues have studied the molecular dynamic of HA using high-speed atomic force microscopy, a technique enabling real-time visualization of molecules on the nanoscale. The researchers were not only able to record the fusogenic transition of HA, but also observe its interaction with exosomes (a lipid bilayer cargo similar to endosome released by cells to outside environment).
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The scientists initially observed the native conformation of HA under neutral physiological buffer, a condition that resembles to a neutral condition in host cell (a pH of 7.6). In this condition, HA was appeared as an ellipsoid, which is in agreement with findings generated by other tools such as X-ray crystallography and cryo-electron microscopy. Wong and colleagues have successfully recorded the fusogenic transition, which happening when HA was exposed to an acidic environment. Their HS-AFM results illustrated a transition of HA from an ellipsoid to a Y-shape together with declination of height and circularity/roundness of HA over time. The researchers reassure the conformational change happens because a particular subunit of HA became easily to be digested by trypsin after the transition.To study how HA can facilitate the fusion between viral membrane and host endosome membrane, Wong and colleagues let HA interacted with exosomes, a lipid bilayer cargo that mimics endosome. The HA-exosome interaction is expected to be similar to HA-endosome interaction during membrane fusion. During the interaction, conformational change of HA was found again before its docked on an exosome. Fusogenic transition releases a particular peptide, known as fusion peptide, which later inserts into the exosomal membrane, enabling the HA molecule to embed on the membrane. The scientists also found evidences that the HA-exosome interaction caused deformation or rupture of exosome, leading to a 'leakage' of exosomal materials.The findings of Wong and coworkers provide important insights for the mechanism of HA-mediated membrane fusion. In addition, their work also demonstrates the advantages of HS-AFM for studying biological processes. Lim and Wong exhilaratingly commented: "This study strongly suggests that HS-AFM is a feasible tool, not only for investigating the molecular dynamic of viral fusion proteins, but also for visualizing the interaction between viral fusion proteins and their target membranes."Influenza A hemagglutinin Influenza A hemagglutinin (HA) is a protein residing on the surface of influenza A virus (the culprit that causes 'the flu' or influenza), playing a key role in viral infectivity. HA's functions include attaching influenza A virus to target cells and viral entry. After the virus attaches to its host cell, it is trapped in a lipid bilayer cargo known as endosome, and subsequently enters into host cytoplasm. This process is called as endocytosis. Acidic environment in endosome triggers structure changes of HA to allow HA to orchestrate fusion between viral membrane and host endosomal membrane. Finally, viral components can be released into host cells and new viruses will be made. The main target cells in human beings are typically located in the upper respiratory tract. Richard Wong from Kanazawa University and colleagues have now applied high-speed atomic force microscopy to study the fusogenic transition of HA, and the interaction of HA with lipid-bilayer membranes.Atomic force microscopy Atomic force microscopy (AFM) is an imaging technique in which the image is formed by scanning a surface with a very small and sharp tip. Horizontal scanning motion of the tip is controlled via piezoelectric elements, while vertical motion is converted into a height profile, resulting in a height distribution of the sample's surface. As the technique does not involve lenses, its resolution is not restricted by the so-called diffraction limit as in X-ray diffraction, for example. In a high-speed setup (HS-AFM), the method can be used to produce movies of a sample's structural changes in real time, as one biomolecule can be scanned in 100 ms or less. Wong and colleagues successfully applied the HS-AFM technique to study the fusogenic transition of HA, and how it fuses with the membranes of biological particles.
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Microbes
| 2,020 |
August 13, 2020
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https://www.sciencedaily.com/releases/2020/08/200813144920.htm
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Researchers discover the microbiome's role in attacking cancerous tumors
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Researchers with the Snyder Institute for Chronic Diseases at the Cumming School of Medicine (CSM) have discovered which gut bacteria help our immune system battle cancerous tumours and how they do it. The discovery may provide a new understanding of why immunotherapy, a treatment for cancer that helps amplify the body's immune response, works in some cases, but not others. The findings, published in Science, show combining immunotherapy with specific microbial therapy boosts the ability of the immune system to recognize and attack cancer cells in some melanoma, bladder and colorectal cancers.
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Dr. Kathy McCoy, PhD, is a leading expert on the body's relationship with the microbiome. She and her team are focused on harnessing the power of the microbiome to improve health and treat diseases. McCoy says to harness and direct that power scientists need to better understand the role bacteria play in regulating the immune system."Recent studies have provided strong evidence that gut microbiota can positively affect anti-tumour immunity and improve the effectiveness of immunotherapy in treating certain cancers, yet, how the bacteria were able to do this remained elusive, " says McCoy, director of the International Microbiome Centre at the University of Calgary and principal investigator on the study. "We've been able to build on that work by showing how certain bacteria enhance the ability of T-cells, the body's immunity soldiers that attack and destroy cancerous cells."First, the researchers identified bacterial species that were associated with colorectal cancer tumours when treated with immunotherapy. Working with germ-free mice, they then introduced these specific bacteria along with immune checkpoint blockade, a type of cancer immunotherapy. Research revealed that specific bacteria were essential to the immunotherapy working. The tumours shrank, drastically. For those subjects that did not receive the beneficial bacteria, the immunotherapy had no effect."We found that these bacteria produce a small molecule, called inosine," says Dr. Lukas Mager, MD, PhD, senior postdoctoral researcher in the McCoy lab and first author on the study. "Inosine interacts directly with T-cells and together with immunotherapy, it improves the effectiveness of that treatment, in some cases destroying all the colorectal cancer cells."The researchers then validated the findings in both bladder cancer and melanoma. The next step in this work will be to study the finding in humans. The three beneficial bacteria associated with the tumours in mice have also been found in cancers in humans."Identifying how microbes improve immunotherapy is crucial to designing therapies with anti-cancer properties, which may include microbials," says McCoy. "The microbiome is an amazing collection of billions of bacteria that live within and around us everyday. We are in the early stage of fully understanding how we can use this new knowledge to improve efficacy and safety of anti-cancer therapy and improve cancer patient survival and well-being."
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Microbes
| 2,020 |
August 13, 2020
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https://www.sciencedaily.com/releases/2020/08/200813142330.htm
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Syphilis may have spread through Europe before Columbus
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Syphilis is a sexually transmitted disease -- and while commonly dismissed due to the availability of modern treatments, it is in fact spreading at an alarming rate: Over the last decades, more than 10 million people around the world have been infected with the syphilis subspecies pallidum of the Treponema pallidum bacteria. Other treponematoses, such as yaws and bejel, are caused by other subspecies of Treponema pallidum. The origins of syphilis, which wreaked havoc in Europe from the late 15th to the 18th century, are still unclear. The most popular hypothesis so far holds Christopher Columbus and his sailors liable for bringing the disease to Europe from the New World.
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The new study indicates a fair possibility that Treponema pallidum already existed in Europe before Columbus ever set sails to America. The researchers found treponematoses in archaeological human remains from Finland, Estonia and the Netherlands. Both molecular dating of the ancient bacterial genomes and traditional radiocarbon dating of the samples were used to estimate the age of the pathogens causing these diseases. The results indicate that the genomes dated back to between the early 15th and 18th century.In addition to the syphilis cases, the researchers found yaws in one of the individuals. Like syphilis, yaws is transmitted via skin contact, although rarely through sexual intercourse. Today, the disease is only found in tropical and subtropical regions. "Our data indicates that yaws was spread through all of Europe. It was not limited to the tropics, as it is today," says last author Verena Schünemann, professor of paleogenetics at the Institute of Evolutionary Medicine of the University of Zurich.The research team also discovered something else: The skeleton found in the Netherlands contained a pathogen belonging to a new, unknown and basal treponemal lineage. This lineage evolved in parallel to syphilis and yaws but is no longer present as a modern-day disease. "This unforeseen discovery is particularly exciting for us, because this lineage is genetically similar to all present treponemal subspecies, but also has unique qualities that differ from them," says first author Kerttu Majander from UZH.Because several closely related subspecies of Treponema pallidum existed throughout Europe, it is possible that the diseases persisted in overlapping regions, and sometimes infected the same patient. The spatial distribution in the northern periphery of Europe also suggests that endemic treponematoses had already spread widely in Europe in the early modern period."Using our ancient genomes, it is now possible for the first time to apply a more reliable dating to the treponema family tree," says Schünemann. The genetic analyses conducted in this study suggest that the predecessor of all modern Treponema pallidum subspecies likely evolved at least 2,500 years ago. For venereal syphilis in particular, the latest common ancestor existed between the 12th and 16th century.According to the newly discovered diversity of treponematoses in early modern Europe, syphilis may have either originated or perhaps further developed in the Old World. "It seems that the first known syphilis breakout cannot be solely attributed to Columbus' voyages to America," concludes Schünemann. "The strains of treponematoses may have co-evolved and interchanged genetic material before and during the intercontinental contacts. We may yet have to revise our theories about the origins of syphilis and other treponemal diseases."
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Microbes
| 2,020 |
August 13, 2020
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https://www.sciencedaily.com/releases/2020/08/200813131259.htm
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Sustainable nylon production made possible by bacteria discovery
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Nylon manufacture could be revolutionised by the discovery that bacteria can make a key chemical involved in the process, without emitting harmful greenhouse gases.
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Scientists have developed a sustainable method of making one of the most valuable industrial chemicals in the world -- known as adipic acid -- which is a key component of the material.More than two million tonnes of the versatile fabric -- used to make clothing, furniture and parachutes -- is produced globally each year, with a market value of around £5 billion.Industrial production of adipic acid relies on fossil fuels and produces large amounts of nitrous oxide -- a greenhouse gas three hundred times more potent than carbon dioxide. A sustainable production method is urgently required to reduce the damage caused to the environment, the team says.Scientists from the University of Edinburgh altered the genetic code of the common bacteria E.coli in the lab. The modified cells were grown in liquid solutions containing a naturally occurring chemical, called guaiacol, which is the main component of a compound that gives plants their shape.Following a 24-hour incubation period, the modified bacteria transformed the guaiacol into adipic acid, without producing nitrous oxide.The environmentally friendly approach could be scaled up to make adipic acid on an industrial scale, researchers say.The study is published in Lead author Jack Suitor, a PhD student in the University of Edinburgh's School of Biological Sciences, said the team is continually exploring new ways of using bacteria to produce chemicals.He said: "I am really excited by these results. It is the first time adipic acid has been made directly from guaiacol, which is one of the largest untapped renewable resources on the planet. This could entirely change how nylon is made."Dr Stephen Wallace, Principle Investigator of the study, and a UKRI Future Leaders Fellow suggested microbes could help solve many other problems facing society.He said: "If bacteria can be programmed to help make nylon from plant waste -- something that cannot be achieved using traditional chemical methods -- we must ask ourselves what else they could do, and where the limits lie. We are all familiar with the use of microbes to ferment food and beer -- now we can ferment materials and medicines. The possibilities of this approach to create a sustainable future are staggering."
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Microbes
| 2,020 |
August 13, 2020
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https://www.sciencedaily.com/releases/2020/08/200813100639.htm
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Virus uses decoy strategy to evade immune system
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University of Otago researchers have learnt more about how viruses operate and can evade the immune system and are now using their discovery to help learn more about COVID-19.
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The recent research, led by Dr Mihnea Bostina and PhD student Sai Velamoor from the Department of Microbiology and Immunology and Otago Micro and Nano Imaging, Electron Microscopy, specifically looked at the Oryctes rhinoceros nudivirus (OrNV) virus, an important biocontrol agent against the coconut rhinoceros beetle, a devastating pest for coconut and oil palm trees in Southeast Asia and the Pacific Islands.The Otago scientists found the virus used a "decoy" strategy to evade the immune system. Dr Bostina explains the findings are a small step in the bid to better understand infectious disease.The research team is now using the same technique to investigate changes in cells infected with SARS-CoV-2, the coronavirus that causes COVID-19."We have used the same technique to investigate changes in cells infected with SARS-CoV-2 and are continuing work in this area."Dr Bostina explains that viruses that replicate and assemble inside the nucleus have evolved special approaches to modify the nuclear landscape for their advantage. The research team used electron microscopy to investigate cellular changes occurring during nudivirus infection and found a unique mechanism for how the virus works."Our study revealed that the virus acquires a membrane inside the nucleus of the infected cell and it gets fully equipped to infect new cells at this precise location. This is in contrast with other enveloped viruses -- like coronavirus, which is also an enveloped virus -- which derive their membranes from other cellular compartments."After it gets fully assembled, the virus uses a clever tactic of passing through different environments, packed inside various membrane structures until it gets released at the cellular membrane."Ms Velamoor says this strategy implies that many of the viruses released by the infected cells will be enclosed in a cellular membrane while travelling inside the infected organism."This means they will be missed by the immune system and they can use this membrane decoy to penetrate any other type of cells, without the need of a virus specific receptor."It shows for the very first time a clever strategy available to insect viruses. It will be interesting to find in what measure other types of viruses -- like the ones infecting humans -- are also capable of carrying out a similar process."Dr Bostina says the research demonstrates another manner in which viruses are capable of hijacking infected cells and alerts scientists to the novel mechanism of viral transmission."Viruses will never cease to amaze us with their indefatigable arsenal of tricks. Only by studying them can we be prepared to adequately respond when they infect us."
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Microbes
| 2,020 |
August 12, 2020
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https://www.sciencedaily.com/releases/2020/08/200812161333.htm
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Swallowing this colonoscopy-like bacteria grabber could reveal secrets about your health
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Your gut bacteria could say a lot about you, such as why you're diabetic or how you respond to certain drugs.
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But scientists can see only so much of the gastrointestinal tract to study the role of gut bacteria in your health. What comes out of you is just a small sample of these bacteria, without indicating where they came from in the digestive system.Purdue University researchers built a way to swallow a tool that acts like a colonoscopy, except that instead of looking at the colon with a camera, the technology takes samples of bacteria.The technology could also move throughout the whole GI tract, not just the colon. This tract, in addition to the colon, includes the mouth, esophagus, stomach, pancreas, liver, gallbladder, small intestine and rectum.Essentially, this tool would make it possible to conduct a "gut-oscopy.""It's all about being able to take samples of bacteria anywhere in the gut. That was impossible before," said Rahim Rahimi, a Purdue assistant professor of materials engineering.The tool is a drug-like capsule that passively weasels through the gut without needing a battery. A pill version of a colonoscopy is already commercially available to view areas of the colon that a traditional colonoscopy can't see, but neither tool can sample bacteria."If a colonoscopy or camera pill sees blood, it can't sample that area to investigate further. You could just sample bacteria from a person's fecal matter, but bacteria can vary a lot throughout the GI tract. Our approach could be complementary," Rahimi said.The bacteria-sampling capsule also would be a lot cheaper, each costing only about a dollar, he estimates.Rahimi's team is working on testing this capsule in pigs, which have a similar GI tract to humans. An initial demonstration of the prototype is published in The researchers 3D-printed the capsule out of resin, the same material used in dental molds and implants. This material would need to be slightly modified for humans to ingest, but is otherwise nontoxic, Rahimi said.When exposed to the pH of a certain gut location, the capsule's biodegradable cap dissolves. Inside the capsule, a hydrogel similar to those used in diapers expands and collects intestinal fluid containing bacteria. Pressure closes shut the capsule's aperture when the sampling is complete, kind of like a plunger.The researchers have tested the prototype capsule in a culture solution designed to simulate the gut bacterial flora of a GI tract. They also tested the capsule's ability to protect the sampled bacteria in different extreme environments. Their experiments so far show that the capsule could successfully sample bacteria common in the gut, such as E. coli, within an hour.In a human, the capsule would continue to move throughout the GI tract with other fecal matter. A scientist could then recover the capsule from a study participant's fecal matter, unscrew the capsule, and study the collected bacteria."This approach is providing new opportunities to study what type of bacteria are present in the gut. It would help us figure out how to manipulate these bacteria to combat disease," Rahimi said.A patent has been filed for this technology through the Purdue Research Foundation Office of Technology Commercialization. The work is funded by Eli Lilly and Company and Purdue's School of Materials Engineering. Rahimi's team is conducting this research at the Birck Nanotechnology Center in Purdue's Discovery Park.Gut microbiota plays an important role in host physiology such as obesity, diabetes, and various neurological diseases. Thus, microbiome sampling is a fundamental approach towards better understanding of possible diseases. However, conventional sampling methods, such as endoscopies or colonoscopies, are invasive and cannot reach the entire small intestine. To address this need, a battery-less 3D-printed sampling capsule, which can collect microbiome samples throughout the entirety of the GI tract was designed. The capsule (9 mm × 15 mm) consists of a 3D printed acrylic housing, a fast-absorbing hydrogel, and a flexible PDMS membrane. Fluids containing samples of the microbial flora within the GI tract enter the device through a sampling aperture on the cap of the device. Once the microbiome enters the housing, the hydrogel absorbs the fluid and swells, effectively protecting the samples within its polymeric matrix, while also pushing on the flexible PDMS membrane to block the sampling aperture from further fluid exchange. The retrieved capsule can be readily disassembled due to the screw-cap design of the capsule and the hydrogel can be removed for further bacterial culture and analysis. As a proof of concept, the capsule's bacterial sampling efficiency and the ability to host microbial samples within the hydrogel in a sealed capsule were validated using a liquid culture containing Escherichia coli. The demonstrated technology provides a promising inexpensive tool for direct sampling and assessment of microbes throughout the GI tract and can enable new insights into the role of diet in mediating host-microbe interactions and metabolism.
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Microbes
| 2,020 |
August 12, 2020
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https://www.sciencedaily.com/releases/2020/08/200812153642.htm
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Human milk based fortifiers improve health outcomes for the smallest premature babies
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More than 380,000 babies are born prematurely in the United States each year, according to the March of Dimes. "Preemies" can be severely underweight babies and struggle to get the nutrients they need from breast milk alone, so neonatal intensive care units provide an additional milk fortifier, either in the form of cow's milk or manufactured from donor breast milk, to keep them healthy.
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Now, a new research study from the University of Missouri and University College in London suggests that using a human-based milk fortifier has better health outcomes for severely underweight, premature babies compared to traditional, cow-based milk fortifiers.Jan Sherman, a professor in the MU Sinclair School of Nursing, collaborated with Alan Lucas, a professor at University College in London, to perform a meta-analysis on various studies involving more than 450 severely underweight, premature babies in the United States, Canada and Austria who received either traditional cow-based milk fortifiers or human-based milk fortifiers.By comparing their health outcomes, they found that the babies who were fed cow milk fortifiers were more than three times as likely to develop necrotizing enterocolitis, a life-threatening intestine disease, and more than twice as likely to develop retinopathy of prematurity, an eye disorder that can lead to blindness."Everyone wants what's best for these underweight, premature babies, and choosing the best type of milk fortifiers for feeding can help lead to improved health outcomes," said Sherman. "Nearly half of neonatal intensive care units in the United States, including the one at MU Children's Hospital, are already using human-based milk fortifiers. If we can reduce these cases of necrotizing enterocolitis, if we can preserve their eye sight and reduce the risk of infection, that will benefit the babies' health in the long term."Neonatal intensive care units can use this research in evaluating the nutritional supplements they give to severely underweight, premature babies, who have a higher risk of death or disease than babies born after a full nine-month pregnancy."Our research is geared toward better understanding if we can avoid cow's milk fortifiers while still feeding premature infants well," said Lucas. "The most current evidence suggests that a diet with entirely human milk and enriched feeds manufactured from donated human milk will meet the nutritional needs of the baby without the potential negative health effects that can come with a cow milk fortifier."
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Microbes
| 2,020 |
August 12, 2020
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https://www.sciencedaily.com/releases/2020/08/200812144114.htm
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Oxygen therapy harms lung microbiome in mice
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One of the hallmarks of severe COVID-19 is shortness of breath and significantly reduced levels of oxygen in the blood, called hypoxemia. Upon hospitalization, these patients are administered oxygen in an attempt to bring their levels back up to normal. However, a new study hints that this universal therapy may have unintended consequences via an unexpected source -- the microbiome.
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"It had been assumed that the lungs were relatively clean and free of bacteria," says Shanna Ashley, Ph.D., a former Post-Doctorate Fellow with the Division of Pulmonary and Critical Care Medicine at U-M Medical School. "We now know that the balance of bacteria inside the lungs matters much like it does in the gut." Ashley worked with a team led by Robert Dickson, M.D., Assistant Professor of Pulmonary & Critical Care Medicine and Microbiology and Immunology, whose lab has spent years exploring the role of the lung microbiome in health and disease. Their work has found that oxygen disrupts this balance, contributing to lung injury.Scientists have long known that oxygen can damage the lungs. "Oxygen is actually a potent lung toxin," says Dickson. "If I put healthy mice in 100% oxygen, they will die in five days, and they'll have the same kind of severe lung injury that patients with COVID-19 or other lung damage have."Patients in intensive care are often treated with high concentrations of oxygen for long periods of time. Their team began to explore how therapeutic oxygen was affecting the lung microbiome. They looked at critically ill patients who were on a ventilator for more than 24 hours and studied bacteria detected in specimens from their lungs. They found marked differences in the bacteria species present in samples from patients depending on whether they received low, intermediate, or high concentrations of oxygen. Specifically, patients who received high oxygen concentrations were much more likely to grow Staphylococcus aureus, bacteria that are very oxygen-tolerant and a common cause of lung infections in the ICU."Different types of bacteria vary quite a bit from each other in how well they can handle oxygen," Dickson says, "So we wondered if the oxygen we give our patients might be influencing the bacterial communities in their respiratory tract."To better understand the relationship between oxygen and lung bacteria, the team designed a series of experiments in mice. They first exposed healthy mice to high concentrations of oxygen to determine the effects of oxygen on the lung bacteria of healthy mice."When we gave high concentrations of oxygen to healthy mice, their lung communities changed quickly, and just like we predicted," said Ashley. "The oxygen-intolerant bacteria went down, and the oxygen-tolerant bacteria went up." After three days of oxygen therapy, oxygen-tolerant Staphylococcus was by far the most commonly detected bacteria in mouse lungs.The team next designed experiments to answer a key "chicken or the egg" question: do these altered bacterial communities contribute to lung injury? Or are bacterial communities altered because the lung is injured? They first addressed this by comparing the relative timing of changes in lung bacteria as compared to the onset of lung injury.Using mice, they were able to demonstrate that while the lung microbiome was changed by high oxygen concentrations after only a day, lung injury wasn't detectable until after 3 days, proving that damage to the lung followed the disruption of the microbiome, and not the other way around. Furthermore, they showed that natural variation in lung bacteria was strongly correlated with variation in the severity of inflammation in oxygen-exposed mice.To further strengthen the causal link, they turned to germ-free mice, which completely lack a microbiome. "We wanted to see whether there was a selective advantage or disadvantage to having bacteria-free lungs when exposed to therapeutic oxygen," says Ashley. When comparing two groups of genetically identical mice -- one with bacteria and one without -- the mice without bacteria were protected from oxygen-induced lung injury."That was an extraordinary finding for us," said Dickson. "Compared to conventional mice, these germ-free mice have the same genetics and receive the same oxygen dosing, but their lungs are protected from injury. Nothing in our current understanding of oxygen-induced lung injury can explain that finding.""It really makes the case that the microbiome is somehow playing a role in lung injury," said Ashley.Critically ill patients receiving oxygen are typically administered antibiotics as well. The team wondered: Could antibiotics alter the severity of oxygen-induced lung injury in mice? "The short answer is yes, we can affect the severity, but it wasn't in the direction we predicted," says Dickson. Vancomycin, an antibiotic that targets gram-positive bacteria like Staphylococcus, had no effect on lung injury, while ceftriaxone, a gram-negative antibiotic, made things worse."The microbiome is not all good and not all bad," comments Dickson. "That's why it's important for us to figure out the mechanisms here. We're currently using very non-specific interventions, when what we need is targeted manipulation of the microbiome."Ashley agrees. "We need to think about using the microbiome as a therapeutic target to prevent doing further damage to patients' lungs while they are on a ventilator or receiving oxygen."Dickson cautions against changing clinical practice prematurely based on these findings. "The question of how much oxygen to give critically ill patients is a complex one, and a topic of intense study," says Dickson. "Our findings are exciting, but I still look to randomized controlled trials to inform my decisions about how to dose oxygen in sick patients."James Kiley, director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, agrees. "This study provides important insights into the contributions of the microbiome toward inflammation and damage in lungs exposed to varying levels of oxygen, and supports the continued importance of understanding how the microbiome and related factors impact lung disease and clinical outcomes."Funding for this study was provided by the National Institutes of Health/National Heart, Lung, and Blood Institute.
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Microbes
| 2,020 |
August 12, 2020
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https://www.sciencedaily.com/releases/2020/08/200812115250.htm
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New way to make bacteria more sensitive to antibiotics discovered
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Researchers from Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have discovered a new way to reverse antibiotic resistance in some bacteria using hydrogen sulphide (H2S).
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Growing antimicrobial resistance is a major threat for the world with a projected 10 million deaths each year by 2050 if no action is taken. The World Health Organisation also warns that by 2030, drug-resistant diseases could force up to 24 million people into extreme poverty and cause catastrophic damage to the world economy.In most bacteria studied, the production of endogenous H2S has been shown to cause antibiotic tolerance, so H2S has been speculated as a universal defence mechanism in bacteria against antibiotics.A team at SMART's Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) tested that theory by adding H2S releasing compounds to Acinetobacter baumannii -- a pathogenic bacteria that does not produce H2S on its own. They found that rather than causing antibiotic tolerance, exogenous H2S sensitised the A. baumannii to multiple antibiotic classes. It was even able to reverse acquired resistance in A. baumannii to gentamicin, a very common antibiotic used to treat several types of infections.The results of their study, supported by the Singapore National Medical Research Council's Young Investigator Grant, are discussed in a paper titled "Hydrogen sulfide sensitizes Acinetobacter baumannii to killing by antibiotics" published in the journal "Until now, hydrogen sulfide was regarded as a universal bacterial defense against antibiotics," says Dr Wilfried Moreira, the corresponding author of the paper and Principal Investigator at SMART's AMR IRG. "This is a very exciting discovery because we are the first to show that H2S can, in fact, improve sensitivity to antibiotics and even reverse antibiotic resistance in bacteria that do not naturally produce the agent."While the study focused on the effects of exogenous H2S on A. baumannii, the scientists believe the results will be mimicked in all bacteria that do not naturally produce H2S."Acinetobacter baumannii is a critically important antibiotic-resistant pathogen that poses a huge threat to human health," says Say Yong Ng, lead author of the paper and Laboratory Technologist at SMART AMR. "Our research has found a way to make the deadly bacteria and others like it more sensitive to antibiotics, and can provide a breakthrough in treating many drug-resistant infections."The team plans to conduct further studies to validate these exciting findings in pre-clinical models of infection, as well as extending them to other bacteria that do not produce H2S.
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Microbes
| 2,020 |
August 12, 2020
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https://www.sciencedaily.com/releases/2020/08/200812094849.htm
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Secretion of sugar polymers modulates multicellularity in the bacterium Myxococcus xanthus
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Research by INRS (Institut National de la Recherche Scientifique) Professor Salim Timo Islam and his PhD student Fares Saïdi has recently revealed that multicellular physiology in the social bacterium Myxococcus xanthus -- a bacterium that can actively reorganize its community according to the environment in which it is found -- is modulated by the secretion of two natural sugar polymers in separate zones of a swarm. Results from their research, done in collaboration with an international team, have been published in the journal
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Professor Salim Timo Islam has been carrying out research in bacterial physiology for four years, focusing on the interactions of bacterial cells with each other, as well as with underlying surfaces. Along with his PhD student Fares Saïdi, they are investigating the origins of multicellularity. More precisely, their work revolves around the factors that allow cells to multiply, specialize, communicate, interact, and move. These behaviours are all associated with multicellularity as they promote the expansion of a community of cells and the formation of complex structures.Their research has characterized two compounds contributing to multicellularity and the distinct areas of production, for each, within a community. Exopolysaccharide (EPS) is produced more by cells at the periphery of the swarm. Production of the second sugar polymer, a novel biosurfactant (BPS), is enriched toward the centre of the swarm. "Since the factors contributing to the development of bacterial communities remain poorly understood, it is very exciting to have identified another," mentions Professor Islam, a specialist in microbial biochemistry and co-first author of the study along with his PhD student Fares Saïdi.Multicellularity is typically associated with organisms such as fungi, plants, and animals. As part of this study, the researchers studied the basis for this evolutionary transition on a smaller scale: the bacterium Myxococcus xanthus. This organism has the distinction of being able to reorganize the structure of its population, allowing it to react to different environmental signals and even eat other bacteria.In response to a hostile environment, such as in instances of nutrient deficiency, this bacterium directs its homogenous population to specialize into three subtypes of cells. These communities thus form 3-dimensional structures, visible to the naked eye. It is thanks to this multicellular lifestyle that they ensure the survival of their community.
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Microbes
| 2,020 |
August 11, 2020
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https://www.sciencedaily.com/releases/2020/08/200811204527.htm
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Bouncing, sticking, exploding viruses: Understanding the surface chemistry of SARS-CoV-2
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Better understanding of the surface chemistry of the SARS-CoV-2 virus is needed to reduce transmission and accelerate vaccine design.
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Researchers at Michigan Tech, TÜV SÜD UK National Engineering Laboratory and University of Edinburgh call for increased research on virus surface stability and interaction in "Surface Chemistry Can Unlock Drivers of Surface Stability of SARS-CoV-2 in Variety of Environmental Conditions" in the Cell Press journal We're told to wash our hands with soap for 20 seconds to kill viruses. Why? Because the soap interacts with the surface chemistry of a virus, particularly the lipid, or fatty, casing around it, and essentially makes the virus explode.Handwashing is a clear example of why understanding how viruses interact with surface environments is important. Increased research will better equip us to diminish how long viruses survive on surfaces or in the air, an important way to stop the spread."If the surface is not friendly, it's easier for the virus to fall apart. Where the virus has more friendly interactions with the surface, it's more likely to stay infectious," said Caryn Heldt, professor of chemical engineering and director of the Health Research Institute at Michigan Technological University."Viruses have unique ways of interacting with surfaces. The surface chemistry of the virus will change how the virus interacts with water," Heldt said. "If water such as humidity, which is common in your breath and in the air, gets between the virus and a surface, it can really change the way the virus interacts with that surface. The virus surface and the environment: you can't separate them out."Part of the reason the scientific community's understanding of the SARS-CoV-2 virus continues to evolve is because there are only a few techniques available to measure the small amounts of virus particles required to infect a person as compared to other types of biomolecules, such as proteins."We need to understand how viruses interact with surfaces with and without water present, but the traditional ways we think of studying surface chemistry cannot detect these low levels of virus," Heldt said.Heldt and coauthors said their article provides a broad overview of different ways researchers could learn more about these surface interactions on a chemical level.Unlike the viruses that cause influenza, SARS-CoV-2 is mainly transmitted through aerosols, or particles that travel through and stay suspended in the air when people talk, sing, cough or sneeze.The flu is transmitted by large droplets you breathe out, which fall to and stay infectious on surfaces. Heldt said surfaces have not been ruled out as a mode of transmission, but that the most common form of transition seems to be aerosol inhalation. "It's about how close you are to someone and for how long," she said.Temperature and humidity in particular seem to have greater effects on the SARS-CoV-2 virus' virility."For the first time, we highlight potential mechanisms of the novel SARS-CoV-2 surface stability in various environmental conditions including temperature and relative humidity," said Aliakbar Hassanpouryouzband, a postdoctoral research associate at the University of Edinburgh.While viruses are typically more stable when it's colder, which explains why flu season hits during the winter, that doesn't seem to be the case for the virus that causes COVID-19. However, researchers can infer from what heat does to molecules -- it increases their energy, causing them to move and vibrate more quickly -- that increased vibrations of virus molecules causes them to explode and no longer be infectious.When it comes to humidity, viruses need to bind some water to their surfaces. But dehydrating a virus molecule isn't a cut-and-dried solution -- it can actually make some molecules more stable.Along with further research into the effects of humidity, temperature and other environmental conditions, there's a need to explore the effects of pH balance and protein casings on the virus. The work to better understand the surface chemistry of SARS-CoV-2 will help scientists around the world design vaccines for this pandemic and those of the future."We hope that this article will assist experimental scientists worldwide in their investigations for unravelling the molecular drivers implicated in this new coronavirus transmission from the surfaces as well as in vaccine development and antiviral drug design," said Edris Joonaki, fluid properties expert at TÜV SÜD UK National Engineering Laboratory.
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Microbes
| 2,020 |
August 11, 2020
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https://www.sciencedaily.com/releases/2020/08/200811133228.htm
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First oral anthrax vaccine for livestock, wildlife
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There may soon be a new weapon in the centuries-old battle against anthrax in wildlife thanks to groundbreaking work at the Texas A&M University College of Veterinary Medicine & Biomedical Sciences (CVMBS).
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Anthrax, a disease caused by a bacterium called Bacillus anthracis, contaminates surface soil and grasses, where it may be ingested or inhaled by livestock or grazing wildlife. This is especially common in the western Texas Hill Country, where each year the disease kills livestock and wildlife.While normally not an attention-grabbing problem, a spike of cases in 2019 made headlines around the state.According to Dr. Jamie Benn Felix, a postdoctoral research associate in the Cook Wildlife Lab led by CVMBS Department of Veterinary Pathobiology's (VTPB) Dr. Walt Cook, that spike may have been responsible for the deaths of more than 10,000 animals."If you assume the economic value for each animal was $1,000, which is probably extremely low given the number of exotic species on some of the ranches, you're looking at an economic loss of $10 million in just a few months," she said. "And given the problems with reporting cases, it could be significantly higher than that."The good news is that there is already a vaccine for anthrax, which many livestock owners administer annually. Unfortunately, it can only be administered with an injection that is time consuming for livestock and not feasible for wildlife.With that in mind, Benn Felix and the Cook Wildlife Lab team, in collaboration with VTPB researchers Dr. Allison Rice-Ficht and Dr. Thomas Ficht, went to work to attempt to create a formulation to deliver the vaccine orally, which would allow for potential distribution to wildlife. She recently published the results of a pilot study in If successful, they will have developed the first effective oral vaccine against anthrax for wildlife."The preliminary results showed that this concept has potential, so now we are starting up a deer study and we'll see where it goes from there," Benn Felix said.Anthrax is among the oldest enemies of microbiologists, and the current vaccination method -- using what's known as the Sterne strain -- is basically the same as it was 85 years ago when Max Sterne developed it, so an oral vaccine has been a goal for some time.In fact, in the past, many livestock owners trying to save time and effort would pour the vaccine over food, but previous testing by Benn Felix proved the ineffectiveness of this method.The main issue with an oral vaccine is the ability to keep the bacteria alive in the gastrointestinal tract long enough and in the right amount to produce the desired immune activity in the animal. To that end, other efforts have been made with different strains of the bacteria and other mediums, but have thus far not proven effective.Benn Felix's approach is both simpler and more complex -- simpler, because her approach uses the same strain that has been proven effective for decades, but more complex because of the use of a gel-like suspension."Our idea is that with this oral anthrax vaccine, we can get it into a bait of some sort and then easily vaccinate these animals," Benn Felix said. "The formulation that we're using is the same live strain of bacteria from the current commercial vaccine put into a gel-like substance."Benn Felix compared the release of the vaccine in the gel-like substance, technically known as alginate encapsulation, to a common gumball machine."It's the same general idea as those big glass gumball machines you would see in the mall or a store, in which you put a quarter and get a single gumball out," she said. "The gel holds a bunch of the live attenuated bacteria and it gradually releases some of that bacteria over time."Though they're currently still working at a small scale, Benn Felix and her team are keeping an eye to the distant future and considering how this vaccine might be implemented at a larger scale.One example they're looking at is what Dr. Tonie Rocke did at the National Wildlife Health Center in Madison, Wisconsin, with a plague vaccine for prairie dogs."They put their vaccine into a bait that was flavored with peanut butter flavoring," Benn Felix said. "That is the same general idea that we're going for with this; we would just distribute the baits and then see how many were consumed, or we would have trail cameras that would see if there was any non-target species that ate any of it."There are a lot of things that would go into formulating the bait -- making sure the vaccine is still stable and viable when it's in the bait and then seeing how it would affect or be consumed by wildlife or any other wildlife we don't want to have it," she said.Currently, one of Benn Felix's biggest obstacles is a lack of data on exactly how much damage is caused by anthrax in wildlife in Texas. Her team is actively reaching out to ranchers, hunters and other groups across the state in an effort to increase the reporting on anthrax cases."If anthrax outbreaks aren't reported, it appears as if it's not an issue and the federal government and other organizations don't prioritize funding," Benn Felix said. "I didn't realize this was even an issue until I moved to Texas. Reporting outbreaks will help generate critical data about this issue and demonstrate as a fact what we down here already know, which is that it's a huge issue."
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Microbes
| 2,020 |
August 11, 2020
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https://www.sciencedaily.com/releases/2020/08/200811120143.htm
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Malaria discovery could expedite antiviral treatment for COVID-19
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New research into malaria suggests targeting enzymes from the human host, rather than from the pathogen itself, could offer effective treatment for a range of infectious diseases, including COVID-19.
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The study, conducted by an international team and led by RMIT University's Professor Christian Doerig, outlines a strategy that could save years of drug discovery research and millions of dollars in drug development by repurposing existing treatments designed for other diseases such as cancer.The approach shows so much promise it has received government funding for its potential application in the fight against COVID-19.The study, published in It also revealed that drugs developed for cancer, and which inactivate these human enzymes, known as protein kinases, are highly effective in killing the parasite and represent an alternative to drugs that target the parasite itself.Lead author, RMIT's Dr Jack Adderley, said the analysis revealed which of the host cell enzymes were activated during infection, revealing novel points of reliance of the parasite on its human host."This approach has the potential to considerably reduce the cost and accelerate the deployment of new and urgently needed antimalarials," he said."These host enzymes are in many instances the same as those activated in cancer cells, so we can now jump on the back of existing cancer drug discovery and look to repurpose a drug that is already available or close to completion of the drug development process."As well as enabling the repurposing of drugs, the approach is likely to reduce the emergence of drug resistance, as the pathogen cannot escape by simply mutating the target of the drug, as is the case for most currently available antimalarials.Doerig, Associate Dean for the Biomedical Sciences Cluster at RMIT and senior author of the paper, said the findings were exciting, as drug resistance is one of the biggest challenges in modern healthcare, not only in the case of malaria, but with most infectious agents, including a large number of highly pathogenic bacterial species."We are at risk of returning to the pre-antibiotic era if we don't solve this resistance problem, which constitutes a clear and present danger for global public health. We need innovative ways to address this issue," he said."By targeting the host and not the pathogen itself, we remove the possibility for the pathogen to rapidly become resistant by mutating the target of the drug, as the target is made by the human host, not the pathogen."Doerig's team will now collaborate with the Peter Doherty Institute for Infection and Immunity (Doherty Institute) to investigate potential COVID-19 treatments using this approach, supported by funding from the Victorian Medical Research Acceleration Fund in partnership with the Bio Capital Impact Fund (BCIF).Co-investigator on the grant, Royal Melbourne Hospital's Dr Julian Druce, from the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute, was part of the team that were first to grow and share the virus that causes COVID-19, and said the research was an important contribution to efforts to defeat the pandemic.Royal Melbourne Hospital's Professor Peter Revill, Senior Medical Scientist at the Doherty Institute and a leader on Hepatitis B research, said the approach developed by the RMIT team was truly exciting."This has proven successful for other human pathogens including malaria and Hepatitis C virus, and there are now very real prospects to use it to discover novel drug targets for Hepatitis B and COVID-19," he said.The paper is the outcome of an RMIT-led international collaboration with researchers from Monash University in Melbourne, Dr Danny Wilson (University of Adelaide's Malaria Biology Laboratory Head and Burnet Institute), Dr Jean-Philippe Semblat (from French Government agency Inserm, Paris) and Prof Oliver Billker (Umeå University, Sweden and Sanger Centre, UK).
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Microbes
| 2,020 |
August 11, 2020
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https://www.sciencedaily.com/releases/2020/08/200811120103.htm
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Protein uses two antiviral strategies to ward off infections
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To protect humans against infection, a protein called MARCH8 tags the vesicular stomatitis virus (VSV) for destruction while it merely holds HIV hostage, a new study in
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The findings reveal how a single protein can use multiple strategies to defend cells against viral infection. They could also improve our understanding of how HIV overcomes the human immune defence.Previous studies have shown that MARCH8 stops HIV and VSV from entering human cells by targeting the viral proteins that are essential for these viruses to enter cells. But how the protein does this remained unclear. Researchers in Japan suspected that MARCH8 might flag an important VSV envelope protein for destruction by targeting a particular amino acid called lysine."The VSV G-glycoprotein (VSV-G) has a short tail containing five lysines, making it an ideal target," explains senior author Kenzo Tokunaga, Principal Investigator in the Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan. "The HIV envelope glycoprotein (Env), by contrast, has a very long tail with only two lysines, making it harder for MARCH8 to flag it for destruction."To test their idea, Tokunaga and his team, including co-first authors and Postdoctoral Fellows Yanzhao Zhang and Takuya Tada, replaced the five lysines on the tail of VSV-G with five arginines -- another type of amino acid. They also replaced the two lysines on the tail of HIV Env with two arginines. The change allowed VSV-G to escape MARCH8, but not HIV Env. This suggests that MARCH8 targets HIV Env and VSV-G using two different mechanisms.Instead of marking HIV Env for destruction, the team found that MARCH8 holds it hostage, inhibiting its ability to make infectious copies of itself (replicate) and spread to other cells. When they created a mutant version of MARCH8 that lacks a specific pattern of the amino acid tyrosine, they found that HIV Env was able to escape, allowing the virus to replicate. This suggests that the tyrosine pattern in MARCH8 is essential to its HIV defence strategy."Our work may help explain why humans don't develop symptoms when infected with VSV, even though it can make some animals, mostly cows, horses and pigs, very ill," says Tokunaga. "The findings might also explain, at least in part, why HIV is able to hide from the human immune system, causing persistent infections that are difficult to treat."
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Microbes
| 2,020 |
August 11, 2020
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https://www.sciencedaily.com/releases/2020/08/200811120101.htm
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Modelling parasitic worm metabolism suggests strategy for developing new drugs against infection
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Scientists have revealed a way to eradicate parasitic worms by stopping them from using alternative metabolism pathways provided by bacteria that live within them, according to new findings published today in
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The study has identified three potential drugs that are active against the parasitic worm Brugia malayi (B. malayi), a leading cause of disability in the developing world.Latest figures from 2015 suggest an estimated 40 million people in the world have lymphatic filariasis (elephantiatis) caused by worms such as B. malayi, with an estimated one billion people at risk. Current prevention and treatment efforts rely on a small selection of drugs, but these have limited effectiveness and must be taken for 15 years, and there is an emerging threat of drug resistance."One alternative strategy for preventing lymphatic filariasis has been to use traditional antibiotics to target bacteria that live within most filarial worms," explains lead author David Curran, Research Associate at the Hospital for Sick Children (SickKids) in Toronto, Canada. "These bacteria, from the genus Wolbachia, are specific to each worm and are known to be essential for the worms to survive and reproduce."While targeting the Wolbachia bacteria with antibiotics is a viable strategy, Curran adds that long treatment times and the unsuitability of these antibiotics for pregnant women and children prevent their widespread use, and there remains an urgent need to identify novel targets for treatments. In this study, he and his colleagues looked at targeting both the worm and the bacteria by identifying the essential biological processes provided by the bacteria that the worm depends on.To do this, they built a model of all the metabolic pathways that take place in the worm and in its resident bacteria. They then systematically changed different components of the model, such as oxygen levels, glucose levels, and which enzymes were activated, to see the effects on the worm's growth. Their final model included 1,266 metabolic reactions involving 1,252 metabolites and 1,011 enzymes linked to 625 genes.To cope with the different nutrient conditions, the worm adapted its use of different metabolic pathways -- including those provided by the Wolbachia bacteria -- throughout the different stages of its lifecycle. To see which of the metabolic reactions were critical for survival and reproduction, the team removed some of the possible pathways from the model. They identified 129 metabolic reactions that slowed the growth to less than 50% of the baseline level. Of these, 50 were metabolic processes provided by the Wolbachia bacteria.Having identified these essential metabolic reactions, the team searched for drugs that could block crucial molecules involved in activating these reactions, using databases of existing drugs and their targets. They identified three drugs: fosmidomycin, an antibiotic and potential antimalarial drug; MDL-29951, a treatment being tested for epilepsy and diabetes; and tenofovir, which is approved for treating hepatitis B and HIV. These drugs reduced the numbers of Wolbachia bacteria per worm by 53%, 24% and 30%, respectively."We also found that two of the drugs, fosmidomycin and tenofovir, reduced the worm's reproductive ability," explains co-senior author Elodie Ghedin, previously Professor of Biology and Professor of Epidemiology at New York University, and now Senior Investigator at the National Institutes of Health, Maryland, US. "Fosmidomycin also appeared to affect movement in the worms.""All three of the drugs tested appear to act against adult B. malayi worms by affecting the metabolism of the worms themselves or their resident bacteria," concludes co-senior author John Parkinson, Senior Scientist, Molecular Medicine program, SickKids, and Associate Professor, Biochemistry & Molecular and Medical Genetics, University of Toronto. "This validates our model as a realistic construction of the metabolic processes in these debilitating parasites, and suggests that its use may yield further therapeutic targets with more research."
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Microbes
| 2,020 |
August 10, 2020
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https://www.sciencedaily.com/releases/2020/08/200810103322.htm
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Previously undescribed lineage of Archaea illuminates microbial evolution
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In a publication in
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Archaea make up one of the main divisions of life, next to the Bacteria and the Eukaryotes, the latter of which comprise for example fungi, plants and animals. Archaea are a large group of microorganisms that live in all habitats on Earth ranging from soils and sediments to marine and freshwater environments as well as from human-made to host-associated habitats including the gut. In turn, Archaea are now thought to play a major role in biogeochemical nutrient cycles.In a publication in Because of their great resemblance to Bacteria, Archaea were only described as a separate lineage about 40 years ago and were not studied intensely until very recently, when it became possible to sequence DNA directly from environmental samples and to reconstruct genomes from uncultivated organisms. This field of genetic research, generally referred to as metagenomics, has not only revealed that microbial life including the Archaea is much more diverse than originally thought, but also provided data needed to shed light on the function of these microbes in their environments.The newly described Undinarchaeota were discovered in genetic material from marine (Indian, Mediterranean and Atlantic ocean) and aquifer (Rifle aquiver, Colorado River) environments. The authors could show that they belong to a very diverse and until recently unknown group of so-called DPANN archaea. Members of the DPANN include organisms with very small genomes and limited metabolic capabilities, which suggests that these organisms depend on other microbes for growth and survival1,2,3. In fact, the few so far cultivated DPANN archaea are obligate symbionts or parasites that cannot live on their own4."In line with this, the Undinarchaeota seem to lack several anabolic pathways, indicating that they are, too, depend on various metabolites from so far unknown partner organisms," says research leader Anja Spang. "However, Undinarchaeota seem to have certain metabolic pathways that lack in some of the most parasitic DPANN archaea and may be able to conserve energy by fermentation."While DPANN have only been discovered recently, it becomes increasingly clear that they are widespread and that representatives inhabit all thinkable environments on Earth. Yet, little is known about their evolutionary and ecological role. "In some way, some of the DPANN archaea resemble viruses, needing a host organism, likely other archaea or bacteria, for survival," says Spang. "However, and in contrast to viruses, we currently know very little about the DPANN archaea and how they affect food webs and host evolution. It is also unclear whether DPANN are an ancient archaeal lineage that resembles early cellular life or have evolved later or in parallel with their hosts."With their study, the authors could shed more light on the complex evolution of Archaea. "Our work revealed that many DPANN archaea frequently exchange genes with their hosts, which makes it very challenging to reconstruct their evolutionary history," says first author Nina Dombrowski. Tom Williams (Bristol University) adds: "However, we could show that DPANN have probably evolved in parallel with their hosts over a long evolutionary time scale, by identifying and studying those genes that were inherited from parent-to-offspring instead of having been transferred between host and symbiont."Spang expects that certain DPANN including the Undinarchaeota, may be important for biogeochemical nutrient cycles within the oceans and sediments. "One reason that DPANN were discovered relatively recently, is that they were not retained on the filters originally used for concentrating cells from environmental samples due to their small cell sizes." But since their discovery, DPANN turned out to be much more widespread than originally anticipated. Chris Rinke from the University of Queensland: "Prospective research on the Undinarchaeota and other DPANN archaea will be essential to obtain a better understanding of marine biogeochemical cycles and the role symbionts play in the transformation of organic matter."These questions drive some of the prospective projects of Anja Spang. In particular, in collaboration with their NIOZ colleagues Laura Villanueva, Pierre Offre and Julia Engelmann, the authors of the publication Anja Spang and Nina Dombrowski have just sequenced new DNA from water samples from the Black Sea, revealing that Undinarchaeota are present in almost all anoxic depth layers of this basin. Spang says: "These data are a gold mine for the future exploration of the ecology and evolution of these potentially symbiotic Archaea, allowing us to identify their interaction partners and to unravel further secrets about the biology of the Undinarchaeota."
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Microbes
| 2,020 |
August 10, 2020
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https://www.sciencedaily.com/releases/2020/08/200810103247.htm
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New tools in the fight against lethal citrus disease
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Scientists are closer to gaining the upper hand on a disease that has wiped out citrus orchards across the globe. New models of the bacterium linked to the disease reveal control methods that were previously unavailable.
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Metabolic models of organisms are like road maps of cities."They show you all the biological processes, and how they work together," said UC Riverside microbiology professor James Borneman. "They also show you which molecular pathways, if blocked, will kill the organism."In this case, researchers created the first models of the bacterium associated with Huanglongbing or HLB, also known as citrus greening disease. The team's work is described in a new paper published in Nature's npj Systems Biology and Applications.The research team made models for six different strains of the bacterium known as CLas and doing so enabled them to identify as many as 94 enzymes essential for the bacterium's survival. These enzymes can now be considered targets for the creation of new antibacterial treatments.In addition, the team identified metabolites required for the bacteria to grow."Just like when humans break down the food they eat into small components called metabolites, which feed our cells, bacterial cells also require metabolites for their growth," Borneman said.Knowing the metabolites needed for CLas' growth could enable scientists to cultivate it in a laboratory setting. It is not currently possible to grow CLas on its own, hindering scientists' ability to study it and ultimately to manage it.This research project involved a collaboration between UC Riverside, UC San Diego, Texas A&M University, and the U.S. Department of Agriculture. In addition to Borneman, members of the modeling team included UCR plant pathologist Georgios Vidalakis and UCSD systems biologist Karsten Zengler.UC Riverside is at the forefront of efforts to combat Huanglongbing. Other important areas of research include antibacterial development and delivery, immune system fortification in citrus, engineering resistant citrus via a detailed understanding of host-microbe interactions, breeding resistant citrus, and insect management, among others.Because microbes tend to mutate and acquire resistance mechanisms in response to drugs and other efforts to thwart them, Borneman cautions that any one solution to the problem may be short-lived."Microbes almost always adapt to control measures, perpetuating the 'arms race' between pathogens and hosts," Borneman said. "There won't be one thing that will fix this disease. We likely will need to address all three components associated with the disease -- the bacterium, the insect that transmits it, and the citrus plants -- to find a long-lasting solution."To that end, the research team is constructing metabolic models of citrus and the insect, the Asian citrus psyllid."We expect that this multiorganism modeling endeavor will provide new insights into the mechanisms underlying this disease, which will lead to effective and sustainable Huanglongbing management strategies," Borneman said.
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Microbes
| 2,020 |
August 8, 2020
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https://www.sciencedaily.com/releases/2020/08/200808085752.htm
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Curious clues in war between bacteria in cystic fibrosis patients
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Several different kinds of bacteria can cause lung infections in people with cystic fibrosis (CF). Pseudomonas aeruginosa, which can cause pneumonia, typically infects infants or young children and persists for life, while Burkholderia cepacia complex species only infect teenagers and adults. Although Burkholderia infections are rare, when they do take hold, they are deadly. Now, UNC School of Medicine scientists led by Peggy Cotter, PhD, professor in the UNC Department of Microbiology and Immunology, have discovered a reason for this pathogen's apparent age discrimination.
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This research, published in the journal Scientists have wondered for a long time why Burkholderia does not infect infants and young children. First author and former Cotter Lab graduate student Andrew Perault, MPH, PhD, designed and conducted experiments to show that Pseudomonas bacteria isolated from infants and young children use their harpoon-like T6SS to fire toxins at, and kill, competitor bacteria, including Burkholderia."This may be one of the reasons Burkholderia does not take root in young patients," Cotter said. "Andy showed that although Burkholderia also produce T6SSs, they cannot effectively compete with Pseudomonas isolates taken from young CF patients."However, as those Pseudomonas bacteria adapt to living in the lungs of CF patients, they lose their ability to produce T6SSs and to fight with Burkholderia. The Burkholderia, using their own T6SSs, are then able to kill the Pseudomonas and establish infection."We believe the findings of our study, at least in part, may explain why Burkholderia infections are limited to older CF patients," Perault said. "It appears that as at least some strains of Pseudomonas evolve to persist in the CF lung, they also evolve to lose their T6SSs, and hence their competitive edge over Burkholderia, which are then free to colonize the respiratory tract."The scientists think the Burkholderia T6SS is an important factor promoting the ability of these pathogens to infect CF patients. Therefore, researchers could potentially develop therapeutics to target these secretion systems to prevent infections.Moreover, assessing the T6SS potential of resident Pseudomonas populations within the CF respiratory tract may predict susceptibility of patients to potentially fatal Burkholderia infections.
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Microbes
| 2,020 |
August 7, 2020
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https://www.sciencedaily.com/releases/2020/08/200807093758.htm
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How plants distinguish beneficial from harmful microbes
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Legume plants fix atmospheric nitrogen with the help of symbiotic bacteria, called Rhizobia, which colonize their roots. Therefore, plants have to be able to precisely recognize their symbiont to avoid infection by pathogenic microbes. To this end, legumes use different LysM receptor proteins located on the outer cell surface of their roots. In the study published in
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All land plants have LysM receptors that ensure detection of various microbial signals, but how a plant decides to mount a symbiotic or an immune response towards an incoming microbe is unknown. "We started by asking a basic and, maybe at start, naïve question: Can we identify the important elements by using very similar receptors, but with opposing function as background for a systematic analysis?" says Zoltán Bozsoki. "The first crystal structure of a Nod factor receptor was a breakthrough. It gave us a better understanding of these receptors and guided our efforts to engineer them in plants." Kira Gysel adds.The study combines the structure-assisted dissection of defined regions in LysM receptors for biochemical experiments and in planta functional analysis. "To really understand these receptors, we needed to work closely together and combine structural biology and biochemistry with the systematic functional tests in plants," says Simon Boje Hansen. By using this approach, the researchers identified previously unknown motifs in the LysM1 domain of chitin and Nod factor receptors as determinants for immunity and symbiosis. "It turns out that there are only very few, but important, residues that separate an immune from a symbiotic receptor and we now identified these and demonstrate for the first time that it is possible to reprogram LysM receptors by changing these residues," says Kasper Røjkjær Andersen.The long-term goal is to transfer the unique nitrogen-fixing ability that legume plants have into cereal plants to limit the need for polluting commercial nitrogen fertilizers and to benefit and empower the poorest people on Earth. Simona Radutoiu concludes, "We now provide the conceptual understanding required for a stepwise and rational engineering of LysM receptors, which is an essential first step towards this ambitious goal."
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Microbes
| 2,020 |
August 6, 2020
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https://www.sciencedaily.com/releases/2020/08/200806153557.htm
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New insight into the evolution of complex life on Earth
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A novel connection between primordial organisms and complex life has been discovered, as new evidence sheds light on the evolutionary origins of the cell division process that is fundamental to complex life on Earth.
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The discovery was made by a cross-disciplinary team of scientists led by Professor Buzz Baum of University College London and Dr Nick Robinson of Lancaster University.Their research, published in Science, sheds light on the cell division of the microbe Sulfolobus acidocaldarius, which thrives in acidic hot springs at temperatures of around 75?C. This microbe is classed among the unicellular organisms called archaea that evolved 3.5 billion years ago together with bacteria.Eukaryotes evolved about 1 billion years later -- likely arising from an endosymbiotic event in which an archaeal and bacterial cell merged. The resulting complex cells became a new division of life that now includes the protozoa, fungi, plants and animals.Now a common regulatory mechanism has been discovered in the cell division of both archaea and eukaryotes after the researchers demonstrated for the first time that the proteasome -- sometimes referred to as the waste disposal system of the cell -- regulates the cell division in Sulfolobus acidocaldarius by selectively breaking down a specific set of proteins.The authors report: "This is important because the proteasome has not previously been shown to control the cell division process of archaea."The proteasome is evolutionarily conserved in both archaea and eukaryotes and it is already well established that selective proteasome-mediated protein degradation plays a key role in the cell cycle regulation of eukaryotes.These findings therefore shed new light on the evolutionary history of the eukaryotes.The authors summarise: "It has become increasingly apparent that the complex eukaryotic cells arose following an endosymbiotic event between an ancestral archaeal cell and an alpha-proteobacterium, which subsequently became the mitochondria within the resulting eukaryotic cell. Our study suggests that the vital role of the proteasome in the cell cycle of all eukaryotic life today has its evolutionary origins in archaea."
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Microbes
| 2,020 |
August 6, 2020
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https://www.sciencedaily.com/releases/2020/08/200806122833.htm
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How growth rates influence the fitness of bacteria
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Bacteria are survival artists: When they get nutrition, they multiply rapidly, albeit they can also survive periods of hunger. But, when they grow too quickly, their ability to survive is hampered, as studies by a research team at the Technical University of Munich (TUM) on
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"The fitness of bacteria is more complex than expected," explains Ulrich Gerland, professor for the theory of complex biosystems at the Technical University of Munich. The physicist has been studying the survival strategies of The unicellular organisms, which go by the Latin name Escherichia coli and support digestion in the large intestine of mammals, are a popular model organism. They facilitate investigations into the way living beings can adapt to changing environmental conditions."We have known for some time that biological fitness depends on two things: the growth rate when food is available and the ability to survive periods of nutrient deficiency," explains the scientist. "What was not clear is how these two factors are related."For the first time, Gerland and his team have now systematically investigated the extent to which fast or slow growth influences the survivability of Fat bacteria -- poor fitnessSo, a good diet is bad for the fitness of bacteria. But why? To find an answer to this question, the TUM researchers carried out a number of experiments: First, cultures of In the second step, the unicellular organisms were put on a zero diet. Throughout the entire period, the scientists examined whether and how quickly the cells multiplied, and how long they survived.The research showed that regardless of how well or poorly they were previously fed, bacteria stopped reproducing when they were deprived of food. In this "maintenance phase," organisms struggle for bare survival. All available energy sources -- for example, the cellular remains of dead bacteria -- are used to sustain the metabolism.In this extreme situation, many cells die of starvation within a few days. However, the death rate is particularly high among rapidly growing As it turns out, the abundantly fed bacteria have an increased need for energy, as further experiments prove. Surviving times of scarcity is more difficult for organisms with a high energy consumption. "We now understand why evolution doesn't favor the fastest possible reproduction," says Gerland. "The biological fitness that is crucial for the survival of a species builds on a balance between growth and survivability."The research results may find application in the future, for example, to improve the effect of antibiotics: "Applying a carrot and stick principle, intestinal bacteria growth could be stimulated by consuming a sweet dish. This would weaken the bacteria if an antibiotic against an intestinal infection is then administered," explains Gerland. However, it is still too early for concrete recommendations. More research will be necessary.
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Microbes
| 2,020 |
August 6, 2020
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https://www.sciencedaily.com/releases/2020/08/200806101806.htm
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Peptide makes drug-resistant bacteria sensitive to antibiotics again
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Scientists at Nanyang Technological University, Singapore (NTU Singapore) have developed a synthetic peptide that can make multidrug-resistant bacteria sensitive to antibiotics again when used together with traditional antibiotics, offering hope for the prospect of a combination treatment strategy to tackle certain antibiotic-tolerant infections.
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On its own, the synthetic antimicrobial peptide can also kill bacteria that have grown resistant to antibiotics.Every year, an estimated 700,000 people globally die of antibiotic-resistant diseases, according to the World Health Organisation. In the absence of new therapeutics, infections caused by resistant superbugs could kill an additional 10 million people each year worldwide by 2050, surpassing cancer. Antibiotic resistance arises in bacteria when they can recognise and prevent drugs that would otherwise kill them, from passing through their cell wall.This threat is accelerated by the developing COVID-19 pandemic, with patients admitted to hospitals often receiving antibiotics to keep secondary bacterial infections in check, amplifying the opportunity for resistant pathogens to emerge and spread.The NTU Singapore team, led by Associate Professor Kimberly Kline and Professor Mary Chan, developed an antimicrobial peptide known as CSM5-K5 comprising repeated units of chitosan, a sugar found in crustacean shells that bears structural resemblance to the bacterial cell wall, and repeated units of the amino acid lysine.The scientists believe that chitosan's structural similarity to the bacterial cell wall helps the peptide interact with and embed itself in it, causing defects in the wall and membrane that eventually kill the bacteria.The team tested the peptide on biofilms, which are slimy coats of bacteria that can cling onto surfaces such as living tissues or medical devices in hospitals, and which are difficult for traditional antibiotics to penetrate.In both preformed biofilms in the lab and biofilms formed on wounds in mice, the NTU-developed peptide killed at least 90 per cent of the bacteria strains in four to five hours.In separate experiments, when CSM5-K5 was used with antibiotics that the bacteria are otherwise resistant to, more bacteria was killed off as compared to when CSM5-K5 was used alone, suggesting that the peptide rendered the bacteria susceptible to antibiotics. The amount of antibiotics used in this combination therapy was also at a concentration lower than what is commonly prescribed.The findings were published in the scientific journal Assoc Prof Kimberly Kline, a Principal Investigator at the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) at NTU, said: "Our findings show that our antimicrobial peptide is effective whether used alone or in combination with conventional antibiotics to fight multidrug-resistant bacteria. Its potency increases when used with antibiotics, restoring the bacteria's sensitivity to drugs again. More importantly, we found that the bacteria we tested developed little to no resistance against our peptide, making it an effective and feasible addition to antibiotics as a viable combination treatment strategy as the world grapples with rising antibiotic resistance."Prof Mary Chan, director of NTU's Centre of Antimicrobial Bioengineering, said: "While efforts are focussed on dealing with the COVID-19 pandemic, we should also remember that antibiotic resistance continues to be a growing problem, where secondary bacterial infections that develop in patients could complicate matters, posing a threat in the healthcare settings. For instance, viral respiratory infections could allow bacteria to enter the lungs more easily, leading to bacterial pneumonia, which is commonly associated with COVID-19."Antimicrobial peptides, which carry a positive electric charge, typically work by binding to the negatively-charged bacterial membranes, disrupting the membrane and causing the bacteria to die eventually. The more positively charged a peptide is, the more efficient it is in binding to bacteria and thus killing them.However, the peptide's toxicity to the host also increases in line with the peptide's positive charge -- it damages the host organism's cells as it kills bacteria. As a result, engineered antimicrobial peptides to date have met with limited success, said Assoc Prof Kline, who is also from the NTU School of Biological Sciences.The peptide designed by the NTU team, called CSM5-K5, is able to cluster together to form nanoparticles when it is applied to bacteria biofilms. This clustering results in a more concentrated disruptive effect on the bacterial cell wall when compared to the activity of single chains of peptides, meaning it has high antibacterial activity but without causing undue damage to healthy cells.To examine CSM5-K5's efficacy on its own, the NTU scientists developed separate biofilms comprising methicillin-resistant Staphylococcus aureus, commonly known as the MRSA superbug; a highly virulent multidrug-resistant strain of Escherichia coli (MDR E. Coli); and vancomycin-resistant Enterococcus faecalis (VRE). MRSA and VRE are classified as serious threats by the US Centers for Disease Control and Prevention.In lab experiments, CSM5-K5 killed more than 99 per cent of the biofilm bacteria after four hours of treatment. In infected wounds on mice, the NTU-developed antimicrobial peptide killed more than 90 per cent of the bacteria.When CSM5-K5 was used with conventional antibiotics, the NTU team found that the combination approach led to a further reduction in the bacteria in both lab-formed biofilms and infected wounds in mice as compared to when only CSM5-K5 was used, suggesting that the antimicrobial peptide made the bacteria sensitive to the drugs they would otherwise be resistant to.More importantly, the NTU team found that the three strains of bacteria studied (MRSA, VRE and MDR E. coli) developed little to no resistance against CSM5-K5. While MRSA developed low-level resistance against CSM5-K5, this made MRSA more sensitive to the drug it is otherwise resistant to.Prof Chan said: "Developing new drugs alone is no longer sufficient to fight difficult-to-treat bacterial infections, as bacteria continue to evolve and outsmart antibiotics/ It is important to look at innovative ways to tackle difficult-to-treat bacterial infections associated with antibiotic resistance and biofilms, such as tackling the bacteria's defence mechanisms. A more effective and economic method to fight bacteria is through a combination therapy approach like ours."The next step forward for the team is to explore how such a combination therapy approach can be used for rare diseases or for wound dressing.The research on the CSM5-K5 antimicrobial peptide was funded by NTU, the National Research Foundation, the Ministry of Education, and the Ministry of Health.
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Microbes
| 2,020 |
August 5, 2020
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https://www.sciencedaily.com/releases/2020/08/200805110129.htm
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How microbes in 'starter cultures' make fermented sausage tasty
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Microbes in "starter cultures" impart a distinctive tang and longer shelf life to food like sourdough bread, yogurt and kimchi through the process of fermentation. To get a better grasp of how microbes do this in fermented sausages, such as chorizo and pepperoni, researchers reporting in the
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Fatty acids and related compounds can influence the quality of fermented foods. For example, one species of bacteria in sourdough cultures produces a type of fatty acid that increases bread's resistance to mold. Scientists, however, haven't had a good handle on how specific cultures drive the formation of these and other similar compounds in meat, partially because some of the previous studies on meats have not included a bacteria-free control. To better understand the link between microbes and molecules, Nuanyi Liang and colleagues wanted to see how the production of fatty acids within sausages varied depending on the microbial culture used to ferment it.To do so, they prepared the meat three ways. In one method, they included only the bacterium
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Microbes
| 2,020 |
August 3, 2020
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https://www.sciencedaily.com/releases/2020/08/200803140007.htm
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Chlamydia: Greedy for glutamine
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Chlamydia are bacteria that cause venereal diseases. In humans, they can only survive if they enter the cells. This is the only place where they find the necessary metabolites for their reproduction. And this happens in a relatively simple way: the bacteria create a small bubble in the cell and divide in it over several generations.
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What is the decisive step that initiates the reproduction of the bacteria? It has not been known so far. Researchers from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, have now discovered it. This is important because the first step in the reproduction of the pathogens is likely to be a good target for drugs.In the case of Chlamydia, the first step is to reprogram the metabolism of their human host cells. The cells then increasingly import the amino acid glutamine from their environment. If this does not work, for example because the glutamine import system is out of order, the bacterial pathogens are no longer able to proliferate. This was reported by a JMU team led by Dr. Karthika Rajeeve, who has meanwhile been awarded a professorship at the Aarhus University in Denmark, and Professor Thomas Rudel in the journal "Chlamydiae need a lot of glutamine to synthesize the ring-shaped molecule peptidoglycan," explains Professor Rudel, who heads the Chair of Microbiology at the JMU Biocenter. In bacteria, this ring molecule is generally a building material of the cell wall. Chlamydiae use it for the construction of a new wall that is drawn into the bacterial cell during division.Next, the JMU team hopes to clarify the importance of the glutamine metabolism in chronic chlamydiae infections. This might provide information that might help to better understand the development of severe diseases as a result of the infection.Chlamydiae cause most venereal diseases in Germany. The bacteria are sexually transmitted and can cause inflammation in the urethra, vagina or anal area. If an infection is detected in time, it can be treated well with antibiotics.Around 130 million people worldwide are infected with Chlamydia. The biggest problem is that the infection usually proceeds without noticeable symptoms. This makes it easier for the pathogen to spread, this leads to severe or chronic diseases such as cervical and ovarian cancer.
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Microbes
| 2,020 |
July 31, 2020
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https://www.sciencedaily.com/releases/2020/07/200731152735.htm
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Insights on the gut microbiome could shape more powerful, precise treatment
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We may not think about it often, but our gut is home to a complex ecosystem of microorganisms that play a critical role in how we function. The system is delicate -- one small change can cause a major shift in the microbiome, resulting in serious consequences. When a person takes an antibiotic, it can wipe out multiple bacterial species and throw this delicate balance off-kilter.
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"Designing a probiotic cocktail is challenging," said Yang-Yu Liu, PhD, an assistant professor in the Department of Medicine at the Brigham. "All of the species in the cocktail interact within a complicated network. When we look at one species that directly inhibits the growth of The researchers began by modeling a microbial community and simulating the FMT process of treating rCDI. Next, they estimated how effective FMT would be at restoring the recipient's healthy gut microbiota. The team then analyzed real-world data from a mouse model and from human patients to validate the modeling.The theoretical model helped the team predict what factors determine the efficacy of FMT. They learned that FMT efficacy decreases as the species diversity of the infected person's gut microbiome increases. The team also developed an optimization algorithm to design a personalized probiotic cocktail to help individuals with rCDI. The algorithm is based on ecological theory that designs a cocktail with the minimum number of bacterial species, while keeping the complicated ecological network of the species in mind. The personalized probiotic cocktails contain species that are effective inhibitors of "We now have an ecological understanding of FMT -- why it works and why it sometimes fails for rCDI," said Liu. "We can move forward to better understand the efficacy of FMT and how we can use it to treat other diseases associated with disrupted microbiota, such as IBD, autism and obesity."
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Microbes
| 2,020 |
July 31, 2020
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https://www.sciencedaily.com/releases/2020/07/200731160824.htm
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Re-engineering antibodies for COVID-19
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With millions of COVID-19 cases reported across the globe, people are turning to antibody tests to find out whether they have been exposed to the coronavirus that causes the disease. But what are antibodies? Why are they important? If we have them, are we immune to COVID-19? And if not, why not?
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Antibody tests look for the presence of antibodies, which are specific proteins made in response to infections. Antibodies are disease specific. For example, measles antibodies will protect you from getting measles if you are exposed to it again, but they won't protect you from getting mumps if you are exposed to mumps."Antibodies are important because they prevent infection and heal patients affected by diseases," said Victor Padilla-Sanchez, a researcher at The Catholic University of America in Washington D.C. "If we have antibodies, we are immune to disease, as long as they are in your system, you are protected. If you don't have antibodies, then infection proceeds and the pandemic continues."This form of foreign-antibody-based protection is called passive immunity -- short-term immunity provided when a person is given antibodies to a disease rather than producing these antibodies through their own immune system."We're at the initial steps of this now, and this is where I'm hoping my work might help," Padilla-Sanchez said. Padilla-Sanchez specializes in viruses. Specifically, he uses computer models to understand the structure of viruses on the molecular level and uses this information to try to figure out how the virus functions.Severe acute respiratory syndrome (SARS) was the first new infectious disease identified in the 21st century. This respiratory illness originated in the Guangdong province of China in November 2002. The World Health Organization identified this new coronavirus (SARS-CoV) as the agent that caused the outbreak.Now we're in the middle of yet another new coronavirus (SARS-CoV-2), which emerged in Wuhan, China in 2019. COVID-19, the disease caused by SARS-CoV-2, has become a rapidly spreading pandemic that has reached most countries in the world. As of July 2020, COVID-19 has infected more than 15.5 million people worldwide with more than 630,000 deaths.To date, there are not any vaccines or therapeutics to fight the illness.Since both illnesses (SARS-CoV and SARS-CoV-2) share the same spike protein, the entry key that allows the virus into the human cells, Padilla-Sanchez's idea was to take the antibodies found in the first outbreak in 2002 -- 80R and m396 -- and reengineer them to fit the current COVID-19 virus.A June 2020 study in the online journal, "Understanding why 80R and m396 did not bind to the SARS-CoV-2 spike protein could pave the way to engineering new antibodies that are effective," Padilla-Sanchez said. "Mutated versions of the 80r and m396 antibodies can be produced and administered as a therapeutic to fight the disease and prevent infection."His docking experiments showed that amino acid substitutions in 80R and m396 should increase binding interactions between the antibodies and SARS-CoV-2, providing new antibodies to neutralize the virus."Now, I need to prove it in the lab," he said.For his research, Padilla-Sanchez relied on supercomputing resources allocated through the Extreme Science and Engineering Discovery Environment (XSEDE). XSEDE is a single virtual system funded by the National Science Foundation used by scientists to interactively share computing resources, data, and expertise.The XSEDE-allocated Stampede2 and Bridges systems at the Texas Advanced Computing Center (TACC) and Pittsburgh Supercomputer Center supported the docking experiments, macromolecular assemblies, and large-scale analysis and visualization."XSEDE resources were essential to this research," Padilla-Sanchez said.He ran the docking experiments on Stampede2 using the Rosetta software suite, which includes algorithms for computational modeling and analysis of protein structures. The software virtually binds the proteins then provides a score for each binding experiment. "If you find a good docking position, then you can recommend that this new, mutated antibody should go to production."TACC's Frontera supercomputer, the 8th most powerful supercomputer in the world and the fastest supercomputer on a university campus, also provided vital help to Padilla-Sanchez. He used the Chimera software on Frontera to generate extremely high-resolution visualizations. From there, he transferred the work to Bridges because of its large memory nodes."Frontera has great performance when importing a lot of big data. We're usually able to look at just protein interactions, but with Frontera and Bridges, we were able to study full infection processes in the computer," he said. Padilla-Sanchez's findings will be tested in a wet lab. Upon successful completion of that stage, his work can proceed to human trials.Currently, various labs across the world are already testing vaccines."If we don't find a vaccine in the near term we still have passive immunity, which can prevent infection for several months as long as you have the antibodies," Padilla-Sanchez said. "Of course, a vaccine is the best outcome. However, passive immunity may be a fast track in providing relief for the pandemic."Molecular graphics and analyses were performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311.
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Microbes
| 2,020 |
July 30, 2020
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https://www.sciencedaily.com/releases/2020/07/200730123643.htm
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New and unique class of carbohydrate receptors
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Exopolysaccharides (EPS) are surface-exposed carbohydrates that surround and protect bacteria and are involved in biofilm formation, cell-to-cell interactions, immune evasion, and pathogenesis. The structures and compositions of EPS synthesized by different bacteria are highly diverse and therefore a molecular fingerprint.
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EPS also plays an important role for bacterial colonization and symbiosis with plants. Nitrogen-fixing soil bacteria (rhizobia) are recognized on the basis of their EPS when colonizing plant roots, judged compatible or incompatible by their legume host and allowed or denied access accordingly. The single-pass transmembrane Exopolysaccharide receptor 3 (EPR3) is responsible for monitoring EPS."To gain a deeper understanding of the function of this receptor, we needed to know what it looks like," says Jaslyn Wong, who conducted this research at Aarhus University. Unfortunately, attempts to determine the structure of the ligand-binding portion of EPR3 remained unsuccessful for years, but a breakthrough was finally achieved by using llama-derived nanobodies to obtain a crystal of the receptor.The structure revealed that EPR3 stands out from other members of the so-called LysM receptor kinases. EPR3 deviates in its ligand-binding domain from the canonical members of this receptor family and has a fold that is unique and novel for carbohydrate binding proteins."This is a good example of how a structure changes our view on the biology," says Kasper Røjkjær Andersen. "We are now able to demonstrate the existence of a completely new and structurally unique class of carbohydrate receptors and find that this class is conserved in the entire plant kingdom. We did not know this before we obtained the structure and this opens for a lot of exciting biology to understand the role of the receptor."Jaslyn Wong adds: "Research on EPS receptors is still in its infancy, and I am excited about how this knowledge could be used and its potential implications on shaping microbiota for more sustainable agriculture."
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Microbes
| 2,020 |
July 30, 2020
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https://www.sciencedaily.com/releases/2020/07/200730113101.htm
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The enemy within: Safeguarding against the spread of intracellular bacteria
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Melbourne researchers have revealed the multiple, intertwined cell death systems that prevent the spread of the 'intracellular' bacterium Salmonella, an important cause of typhoid fever which kills more than 100,000 people annually.
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The team revealed that the spread of Salmonella is curtailed by the death of infected cells, but surprisingly cells can die in several distinct ways. Although Salmonella continuously seeks to outsmart infected cells by blocking their suicide, cells have evolved impressive 'back-up' strategies to ensure that the infected cell can still die and thus protect the body from Salmonella infection and consequent typhoid fever.The research, published in the journal Many disease-causing bacteria invade cells, surviving and reproducing within the cells and hiding from the body's immune system. Salmonella, a cause of serious food-borne infections, is one such 'intracellular' bacterium. Cells have developed a range of defences against intracellular bacteria, Professor Bedoui said."The rapid death of infected cells is an important protective strategy against intracellular bacteria. This stops the reproduction and spread of the bacteria, and can trigger protective immune defences at the site of the infection, which further control the infection," he said."Many proteins have been thought to be important for driving the death of bacteria-infected cells, which signal within cells and also degrade key components of the cell to bring about its death. However, there has been uncertainty about precisely how bacteria-infected cells die, the key molecules involved, and what this means for controlling an infection," Professor Bedoui said.The team used laboratory models lacking different combinations of cell death proteins to understand their contribution to the control of Salmonella infections, Associate Professor Herold said."We investigated the roles of proteins involved in three key types of cell death: apoptosis, pyroptosis and necroptosis," he said. "While these processes all result in cell death, each occurs differently at the molecular level, and has different consequences for triggering immunity and inflammation."When only one of the three forms of cell death were disabled, there was only a minor impact on how effectively Salmonella infections were controlled -- this showed that cells were not reliant on one specific system, Dr Doerflinger said."When we disabled two or all three forms of cell death, we saw that Salmonella infections were not controlled and the bacteria rapidly spread. This suggested that cells have developed several 'backups' to ensure cell death happens if there is a fault in one cell death pathway. While we only studied Salmonella, we speculate that our findings might be relevant to other intracellular pathogens such as the bacterium that causes tuberculosis," he said.The team also revealed unexpected roles for cell death proteins called caspases, Professor Strasser said. "Until now, certain caspases including two known as 'caspase 1' and 'caspase 8' had very well-defined roles as early triggers of two distinct types of cell death. Our results showed that contrary to current perceptions these caspases can act within the 'other pathway' and even at later, critical stages of cell death when the cell is being dismantled."This is an example of another fail-safe process in the overall cell death machinery that ensures protection against pathogens like Salmonella," he said.The flexibility in how cells can die can be explained by the ongoing battle between animals and disease-causing bacteria."Throughout evolution, both sides have developed new tactics in an 'arms race' for supremacy. Living and multiplying inside cells -- rather than outside -- helped the bacteria avoid immune detection, but animals responded by developing ways for infected cells to undergo altruistic suicide -- which we have revealed is a highly coordinated but flexible system that has several fail-safe mechanisms," Professor Strasser said.The research was supported by the Australian National Health and Medical Research Council, the US Leukemia and Lymphoma Society, Cancer Council Victoria, the Australian Phenomics Network, the Cass Foundation, the Wellcome Trust, the German Research Council and the Victorian Government.
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Microbes
| 2,020 |
July 30, 2020
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https://www.sciencedaily.com/releases/2020/07/200730141357.htm
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Scientists expose fascinating 'compartments' in bacteria
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A review paper by Monash Biomedicine Discovery Institute (BDI), published in the high-impact journal
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The BDI's Professor Trevor Lithgow and Associate Professor Chris Greening, experts in bacterial cell biology and physiology, were invited to review the available scientific literature worldwide to consolidate the latest knowledge of organelles."There was an age-old truism until recently that bacteria were simply a bag of enzymes, the simplest type of cells," Professor Lithgow said. "New developments in nanoscale imaging have shown that internal compartments -- organelles -- make them very complex," he said.Cryoelectron microscopy and super-resolution microscopy have allowed scientists to fathom the workings of bacterial organelles, which typically have a diameter 10,000 times smaller than a pinhead. The BDI has been at the forefront in Australia in adopting and developing the use of these technologies, Professor Lithgow said."It's been a rewarding experience doing this scholarly review and being able to showcase the broad swathe of work that demonstrates the complexity of bacterial cells," he said.Organelles enable bacteria to do extraordinary things. They help bacteria photosynthesise in dimly lit environments, break down toxic compounds like rocket fuel or even orientate themselves relative to the Earth's magnetic field by lining up magnetic iron particles. Some bacteria use gas collected within organelles to control buoyancy to let them rise or go deeper in water, allowing optimal access to light and nutrients for growth and division.Exploring and understanding the intricacies of bacterial cells is not only important for scientific knowledge, but also for biotechnological applications and for addressing global issues of human health."Organelles enable many bacteria to perform functions useful for us, from supporting basic ecosystem function to enabling all sorts of biotechnological advances. But a few pathogens use organelles to cause disease," Associate Professor Greening said. "The deadly pathogen that causes tuberculosis, for example, scavenges fatty molecules from our own bodies and stores them as energy reserves in organelles, helping the pathogen to persist for years in our lungs, compromising treatment and making the emergence of drug resistance likely."Countering drug-resistant infections are key 21st century problems for humans, Professor Lithgow said. "In these times of COVID-19 the death tolls we're seeing for viral infections are terrible, but the projection is that by 2050 at least 22,000 Australians (and 10 million people worldwide) will die every year due to infections caused by drug-resistant bacteria," he said.
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Microbes
| 2,020 |
July 29, 2020
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https://www.sciencedaily.com/releases/2020/07/200729114850.htm
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Antibiotics use early in life increases risk of inflammatory bowel disease later in life
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Even short, single antibiotic courses given to young animals can predispose them to inflammatory bowel disease (IBD) when they are older, according to Rutgers researchers.
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The study, published in "This study provides experimental evidence strengthening the idea that the associations of antibiotic exposures to the later development of disease in human children are more than correlations, but that they are actually playing roles in the disease causation," said study co-author Martin Blaser, director of the Rutgers Center for Advanced Biotechnology and Medicine.To determine if the increased disease risk was due to the disruption of the microbiome from antibiotics, the researchers studied the effects of exposure to dextran sulfate sodium, a chemical known to injure the colon, both in mice that received antibiotics, and in mice that had perturbed microbial contents transplanted into their intestines versus a control group.They found that the mice that received either the antibiotics themselves or received the antibiotic-perturbed microbiome had significantly worse colitis, showing that exposure to antibiotics changed the microbiome, altered the immune response in the colon and worsened the experimental colitis."The use of a well-validated model of colitis enabled us to study the effects of prior antibiotic exposures on the development of an important disease process," said lead author Ceren Ozkul, a visiting scholar from the Department of Pharmaceutical Microbiology at Hacettepe University in Turkey.The study continues Blaser's work on the hypothesis that disrupting the early life microbiome, especially by antibiotics and C-section, is one of the factors driving modern epidemics.
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Microbes
| 2,020 |
July 28, 2020
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https://www.sciencedaily.com/releases/2020/07/200728130831.htm
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Metal-breathing bacteria could transform electronics, biosensors, and more
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When the
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The ability of this bacterium to produce molybdenum disulfide -- a material that is able to transfer electrons easily, like graphene -- is the focus of research published in "This has some serious potential if we can understand this process and control aspects of how the bacteria are making these and other materials," said Shayla Sawyer, an associate professor of electrical, computer, and systems engineering at Rensselaer.The research was led by James Rees, who is currently a postdoctoral research associate under the Sawyer group in close partnership and with the support of the Jefferson Project at Lake George -- a collaboration between Rensselaer, IBM Research, and The FUND for Lake George that is pioneering a new model for environmental monitoring and prediction. This research is an important step toward developing a new generation of nutrient sensors that can be deployed on lakes and other water bodies."We find bacteria that are adapted to specific geochemical or biochemical environments can create, in some cases, very interesting and novel materials," Rees said. "We are trying to bring that into the electrical engineering world."Rees conducted this pioneering work as a graduate student, co-advised by Sawyer and Yuri Gorby, the third author on this paper. Compared with other anaerobic bacteria, one thing that makes "That lends itself to connecting to electronic devices that have already been made," Sawyer said. "So, it's the interface between the living world and the humanmade world that is fascinating."Sawyer and Rees also found that, because their electronic signatures can be mapped and monitored, bacterial biofilms could also act as an effective nutrient sensor that could provide Jefferson Project researchers with key information about the health of an aquatic ecosystem like Lake George."This groundbreaking work using bacterial biofilms represents the potential for an exciting new generation of 'living sensors,' which would completely transform our ability to detect excess nutrients in water bodies in real-time. This is critical to understanding and mitigating harmful algal blooms and other important water quality issues around the world," said Rick Relyea, director of the Jefferson Project.Sawyer and Rees plan to continue exploring how to optimally develop this bacterium to harness its wide-ranging potential applications."We sometimes get the question with the research: Why bacteria? Or, why bring microbiology into materials science?" Rees said. "Biology has had such a long run of inventing materials through trial and error. The composites and novel structures invented by human scientists are almost a drop in the bucket compared to what biology has been able to do."
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Microbes
| 2,020 |
July 28, 2020
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https://www.sciencedaily.com/releases/2020/07/200728130828.htm
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Microbiologists clarify relationship between microbial diversity and soil carbon storage
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In what they believe is the first study of its kind, researchers led by postdoctoral researcher Luiz A. Domeignoz-Horta and senior author Kristen DeAngelis at the University of Massachusetts Amherst report that shifts in the diversity of soil microbial communities can change the soil's ability to sequester carbon, where it usually helps to regulate climate.
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They also found that the positive effect of diversity on carbon use efficiency -- which plays a central role in that storage -- is neutralized in dry conditions. Carbon use efficiency refers to the carbon assimilated into microbial products vs carbon lost to the atmosphere as COShe and colleagues addressed these questions because they point out, "empirical evidence for the response of soil carbon cycling to the combined effects of warming, drought and diversity loss is scarce." To explore further, they experimentally manipulated microbial communities while varying factors such as microbe community species composition, temperature and soil moisture. Details are in In addition to first author Domeignoz-Horta and others at UMass Amherst, the team includes Serita Frey at the University of New Hampshire and Jerry Melillo at the Ecosystems Center, Woods Hole, Mass.They point out that carbon in the soil is regulated in part by the rate and efficiency with which the microbes living there can use fresh plant foods and other parts of soil organic matter to grow. DeAngelis says some "soil carbon pools" can "stick around for decades and turn over very slowly. These are ones we really want to have because they help soil stay spongy to absorb water and help bind and release nutrients for plant growth.""Diversity is interesting, not just in microbiology but in all organisms, including humans," DeAngelis says. "It's controlled by a lot of different factors, and it seems that more diverse systems tend to work more efficiently and to tolerate stress better. We wanted to understand the role of microbial diversity in soil carbon efficiency."She adds, "Replicating diversity is tricky, which is why we used a model system soil. Luiz extracted microbes from soil, made serial dilutions of microbe concentrations in a buffer and inoculated the soil to get variation in diversity." They let the five different microbial mixes grow for 120 days. In addition to other tests, they used a new method based on a heavy, stable isotope of water known as 18O-H"One interesting thing we found is that we do see that more diverse communities are more efficient. The microbes grow more than in less diverse communities, but that increase in growth with diversity is lost when they are stressed for water. This suggests that there's a limit to the stress resilience with high diversity," she adds.The authors point out, "Results indicate that the diversity by ecosystem-function relationship can be impaired under non-favorable conditions in soils, and that to understand changes in soil carbon cycling we need to account for the multiple facets of global changes."DeAngelis adds, "We were a little surprised at how our approach worked so well. I'm really interested in the temperature/moisture efficiencies and Luiz is more interested in the diversity angle. It was a combination of the two that was the most interesting result."
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Microbes
| 2,020 |
July 28, 2020
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https://www.sciencedaily.com/releases/2020/07/200728113545.htm
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Medieval medicine remedy could provide new treatment for modern day infections
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Antibiotic resistance is an increasing battle for scientists to overcome, as more antimicrobials are urgently needed to treat biofilm-associated infections. However scientists from the School of Life Sciences at the University of Warwick say research into natural antimicrobials could provide candidates to fill the antibiotic discovery gap.
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Bacteria can live in two ways, as individual planktonic cells or as a multicellular biofilm. Biofilm helps protect bacteria from antibiotics, making them much harder to treat, one such biofilm that is particularly hard to treat is those that infect diabetic foot ulcers.Researchers at the University of Warwick, Dr Freya Harrison, Jessica Furner-Pardoe, and Dr Blessing Anonye, have looked at natural remedies for the gap in the antibiotic market, and in the paper, 'Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients' published in the journal Scientific Reports today the 28 July, researchers say medieval methods using natural antimicrobials from every day ingredients could help find new answers.The Ancientbiotics research team was established in 2015 and is an interdisciplinary group of researchers including microbiologists, chemists, pharmacists, data analysts and medievalists at Warwick, Nottingham and in the United States.Building on previous research done by the University of Nottingham on using medieval remedies to treat MRSA, the researchers from the School of Life Sciences at University of Warwick reconstructed a 1,000-year-old medieval remedy containing onion, garlic, wine, and bile salts, which is known as 'Bald's eyesalve', and showed it to have promising antibacterial activity. The team also showed that the mixture caused low levels of damage to human cells.They found the Bald's eyesalve remedy was effective against a range of Gram-negative and Gram-positive wound pathogens in planktonic culture. This activity is maintained against the following pathogens grown as biofilms:2. 3. 4. 5. All of these bacteria can be found in the biofilms that infect diabetic foot ulcers and which can be resistant to antibiotic treatment. These debilitating infections can lead to amputation to avoid the risk of the bacteria spreading to the blood to cause lethal bacteremia.The Bald's eyesalve mixtures use of garlic, which contains allicin, can explain activity against planktonic cultures, however garlic alone has no activity against biofilms, and therefore the anti-biofilm activity of Bald's eyesalve cannot be attributed to a single ingredient and requires the combination of all ingredients to achieve full activity.Dr Freya Harrison, from the School of Life Sciences at the University of Warwick comments:"We have shown that a medieval remedy made from onion, garlic, wine, and bile can kill a range of problematic bacteria grown both planktonically and as biofilms. Because the mixture did not cause much damage to human cells in the lab, or to mice, we could potentially develop a safe and effective antibacterial treatment from the remedy."Most antibiotics that we use today are derived from natural compounds, but our work highlights the need to explore not only single compounds but mixtures of natural products for treating biofilm infections. We think that future discovery of antibiotics from natural products could be enhanced by studying combinations of ingredients, rather than single plants or compounds. In this first instance, we think this combination could suggest new treatments for infected wounds, such as diabetic foot and leg ulcers. "Jessica Furner-Pardoe, from the Medical School at the University of Warwick comments:"Our work demonstrates just how important it is to use realistic models in the lab when looking for new antibiotics from plants. Although a single component is enough to kill planktonic cultures, it fails against more realistic infection models, where the full remedy succeeds."In previous research Christina Lee, from the School of English at the University of Nottingham, had examined the Bald's Leechbook, an Old English leatherbound volume in the British Library, to see if it really works as an antibacterial remedy. The Leechbook is widely thought of as one of the earliest known medical textbooks and contains Anglo-Saxon medical advice and recipes for medicines, salves and treatments. Christina adds: "Bald's eyesalve underlines the significance of medical treatment throughout the ages. It shows that people in Early Medieval England had at least some effective remedies. The collaboration which has informed this project shows the importance of the arts in interdisciplinary research."
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Microbes
| 2,020 |
July 27, 2020
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https://www.sciencedaily.com/releases/2020/07/200727145810.htm
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Stopping listeria reproduction 'in its tracks'
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Listeria contaminations can send food processing facilities into full crisis mode with mass product recalls, federal warnings and even hospitalization or death for people who consume the contaminated products. Destroying the bacterium and stopping its spread can be challenging because of the formation of biofilms, or communities of resistant bacteria that adhere to drains or other surfaces.
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Researchers at the University of Houston are reporting in the "The addition of cobalt, a heavy metal, drastically improved the effectiveness of titanium-dioxide because now it works under regular human conditions -- sunlight, fluorescent light such as light bulbs and even in 'the absence of light,' like in a freezer," said Francisco Robles, lead author for the study and associate professor of mechanical engineering technology.Titanium-dioxide has long been an effective catalyst in the chemical industry with many applications, but it has limitations because ultraviolet light is needed to make it work, according to Robles. "UV light sources are in short supply in sunlight and producing it is expensive and a health hazard (e.g. carcinogen), so we set out to find a solution. Making it effective under natural light conditions is significant, and free," he said.A naturally occurring mineral, titanium-dioxide is often used in the food industry as an additive or whitening agent for sauces, dressings and powdered foods and is considered safe by the U.S. Food and Drug Administration. It's also used in sunscreen for its protective effects against UV/UVB rays from the sun.Sujata Sirsat, study co-author and assistant professor at UH's Conrad N. Hilton College of Hotel and Restaurant Management, believes cobalt-doped titanium-dioxide, whether manufactured directly into food packaging or added to food products, could potentially reduce the risk for large listeria outbreaks in food processing environments."Listeria is a rare foodborne pathogen that can survive in refrigerated conditions. So, if you had a contaminated bowl of potato salad, not only can listeria survive, it can increase in numbers potentially causing a serious health issue. The cobalt-doped titanium dioxide can potentially stop the spread in its tracks," said Sirsat, an expert in food safety and public health, who said toxicity testing is needed to determine its safety in food products.An estimated 1,600 people get listeriosis each year from eating foods contaminated with listeria monocytogenes, and about 260 people die, according to the U.S. Centers for Disease Control and Prevention. The CDC has led investigations on 19 multistate listeria monocytogenes outbreaks involving fruits, vegetables, deli meats, cheeses and more since 2011. The infection is most likely to sicken pregnant women and their newborns, adults over 65 and people with weakened immune systems.The researchers believe cobalt-doped titanium-dioxide could have a wide range of applications beyond bacteria control. "You could coat hospital plates with it to make them incapable of forming bacteria or coat the packaging of milk and other dairy products. You could even add it to paint to make bacteria-controlled paint. The possibilities are tremendous," said Robles, who has been studying the effects of the chemical compound for nearly 15 years.
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Microbes
| 2,020 |
July 27, 2020
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https://www.sciencedaily.com/releases/2020/07/200727114659.htm
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Researchers speed up gold-standard COVID-19 diagnostic test
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Clinician-scientists at Nanyang Technological University, Singapore's (NTU Singapore) Lee Kong Chian School of Medicine (LKCMedicine) have demonstrated a way to improve the speed, handling time and cost of COVID-19 laboratory tests. The improved testing method yields results in 36 minutes -- a quarter of the time required by existing gold-standard tests.
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Their new approach could enable the wider adoption of COVID-19 testing for diagnosis in academic or research laboratories, and allow for screening and research especially in countries and regions with limited laboratory capabilities. The test, which can be done with portable equipment, could also be deployed in the community as a screening tool.Currently, the most sensitive method for testing for COVID-19 is through a laboratory technique called polymerase chain reaction (PCR), in which a machine amplifies viral genetic material by copying it over and over again so any trace of the SARS-CoV-2 virus can be detected.A big bottleneck in sample testing is RNA purification -- separating RNA from other components in the patient sample -- a laborious process that requires chemicals that are now in short supply worldwide. Its steps have to be performed by highly trained technical staff and can take a few hours. Currently, automated equipment for sample preparation costs hundreds of thousands of dollars, and requires specialised laboratory facilities.The method developed by NTU LKCMedicine combines many of these steps and allows direct testing on the crude patient sample, cutting down the turnaround time from sample-to-result, and removing the need for RNA purification chemicals.Details of the new approach were published in the scientific journal Mr Wee Soon Keong, a PhD candidate at NTU LKCMedicine and the first author of the paper, said: "While polymerase chain reaction (PCR) is a venerable technology that has proven to be a workhorse for biological research, it has some drawbacks when used outside of the laboratory environment. The process is fiddly and time-consuming. Our rapid COVID-19 test involves a single-tube reaction that reduces hands-on time and biosafety risk for lab personnel, as well as the likelihood for carryover contamination during the processing of samples."Aside from testing for COVID-19, the same method developed by the NTU LKCMedicine team can also be used to detect other viruses and bacteria, including the dengue virus, which is set to plague Singapore as the country braces itself for one of the worst dengue outbreaks amid the coronavirus pandemic.Leader of the research team, Associate Professor Eric Yap, who also heads the Microbial Genomics Laboratory, said: "We previously demonstrated that this method works for dengue virus as well. When used directly on a crude blood sample with dengue virus, the test yielded results in 28 minutes. As Singapore battles the dual outbreak of dengue and COVID-19, both with similar early symptoms, our test could help in differentiating between the two infectious diseases."Professor James Best, Dean of NTU LKCMedicine, said: "As Singapore continues with proactive testing to detect, isolate, and contain the possible spread of the coronavirus, rapid portable screening tools like the one developed by Assoc Prof Yap and his team could come in handy at testing sites in the community, allowing for infected patients to be identified quickly, and swift action to be taken to prevent transmission."Typically, in PCR tests, the genetic material on a swab sample collected from a patient has to be extracted to remove any substances in the sample that prevent the PCR test from working. An example of an inhibitor in respiratory samples is mucin (a main component of mucus).The test designed by the NTU LKCMedicine team, which includes senior research fellow Dr Sivalingam Paramalingam Suppiah, uses the 'direct PCR' method, removing the need for RNA purification, a time-consuming and costly step. Instead, they added inhibitor-resistant enzymes and reagents targeting compounds that obstruct RNA amplification, such as mucin, a main component of mucus. These enzymes and reagents, which are commercially available, have high resistance to such compounds that otherwise inhibit PCR, rendering the test inaccurate.The biochemical mix of crude sample and inhibitor-resistant enzymes and reagents is placed into a single tube, which is inserted into a laboratory thermocycler, a machine used to amplify genetic material in PCR. After 36 minutes, results reveal whether there is any trace of COVID-19 with confidence."By skipping the RNA extraction step with our direct-PCR method, we see cost savings on nucleic acid extraction kits, and avoid the problem of reagents in short supply when lab testing is ramped up and the demand increases globally," said Dr Sivalingam.The team also tested this method on a portable thermocycler, which can be deployed in low-resource settings and endemic areas, pointing to the possibility of having this test done in community healthcare settings by frontline healthcare workers.Assoc Prof Yap said: "We are now trying to deploy such direct-PCR methods, developed by ourselves and others, for routine diagnostics. We need to determine the actual utility and benefits in a real-world setting, and to understand if there are any trade-offs. When one bottleneck is removed, other challenges may emerge -- like ensuring quality control, or reducing manual errors."The team is now looking to use this method for COVID-19 testing at the NTU Clinical Diagnostic Laboratory at LKCMedicine that Assoc Prof Yap heads."Our goal is to develop ultrafast and automated tests that yield results in minutes, and that can be performed by healthcare workers in the clinic with similar accuracy and sensitivity as in specialised laboratories. This will allow us to take PCR testing out of conventional laboratories nearer to the point-of-care, and into the low-resource settings that need them the most," he said.
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Microbes
| 2,020 |
July 24, 2020
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https://www.sciencedaily.com/releases/2020/07/200724104230.htm
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High levels of antibiotic-resistant bacteria found on equipment in communal gyms
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Research presented at ASM Microbe Online found that 43% of Staphylococcus bacteria found on exercise equipment in university gyms were ampicillin-resistant, with 73% of those isolates being resistant to multiple additional drugs. The late Xin Fan, Ph.D., and her student Chase A. Weikel of West Chester University (WCU) conducted the research in cooperation with WCU's John M. Pisciotta, Ph.D., associate professor of Biology.
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According to the U.S. Centers for Disease Control and Prevention, roughly 120,000 S. aureus bacteremia cases resulted in 20,000 deaths in 2017. Skin abrasions are a common route of entry of pathogenic S. aureus strains. As highlighted by the ongoing COVID-19 pandemic, there is increasing public concern regarding communal areas as a bastion of infectious microorganisms.Results of the study found 43% of 462 S. aureus isolates recovered from 45 different exercise equipment surfaces were ampicillin resistant. Of 60 representative ampicillin-resistant isolates, 73% were resistant to two or more additional drugs including erythromycin and sulfisoxazole."These results suggest regularly contacted surfaces in different recreational environments can harbor multi-drug resistant S. aureus (MDRSA) and should be disinfected frequently to best maintain public health and community wellbeing," said Chase A. Weikel, a 2018 graduate of West Chester University and current graduate student at Thomas Jefferson University in Philadelphia.Samples were collected from 2 university recreational facilities. The surfaces gym patrons frequently touched, including dumbbells and barbell handles, cable pull grips, kettlebells, elliptical and treadmill handles were swabbed and plated on Mannitol Salt Agar (MSA). This selective and differential media was used to isolate and presumptively identify S. aureus. Isolates were replicated to MSA plus ampicillin. Isolates additionally resistant to oxacillin or penicillin were subsequently screened using CHROMagar™ MRSA; a sensitive and specific media used to screen for methicillin-resistant S. aureus (MRSA). Isolates that tested positive using CHROMagar™ were subjected to additional confirmatory methods including latex agglutination assay. Microscopy was used to confirm Gram-positive status and cellular morphology and arrangement.This research is being presented as an ePoster at the ASM Microbe conference which is proceeding in an on-line format in August 2020. ASM Microbe Online brings you the dynamic, cutting-edge science of ASM Microbe 2020, the annual meeting of the American Society for Microbiology. Explore the latest research in the microbial sciences with ePosters, hear from experts in the field during live keynotes and access track-related content with a curated selection of on-demand sessions.
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Microbes
| 2,020 |
July 23, 2020
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https://www.sciencedaily.com/releases/2020/07/200723143752.htm
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Highly stable amyloid protein aggregates may help plant seeds last longer
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Highly stable polymeric "amyloid" proteins, best known for their role in Alzheimer's disease, have been mostly studied in animals. But a new study on the garden pea publishing July 23, 2020 in the open-access journal
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Amyloid is a type of protein conformation in which adjacent sheets of amino acids are bound together to form aggregates that are highly resistant to degradation. In animals, amyloids play roles in hormone storage and long-term memory formation, among other activities, but are best known from Alzheimer's disease, which is characterized by the formation of plaques of amyloid aggregates in the brain.Direct evidence that plants form amyloids has been limited, but recent biochemical experiments have hinted at it, and a recent bioinformatic study led by Nizhnikov turned up a group of seed storage proteins with amino acid sequences that suggested they might be able to form amyloids.In the new study, working in the garden pea, the researchers extracted the seed storage proteins, including one called vicilin, and analyzed both the full-length protein and two its domains called cupins that are rich in predicted amyloidogenic regions. When the genes were engineered into bacteria, all three proteins formed amyloid fibrils resistant to strong detergents; they also bound amyloid-specific dyes, and displayed unique spectral properties, all indicative of bona fide amyloid structure.In vivo, in the pea seed, the authors used an amyloid-specific dye and an antibody to vicilin to show that the two co-localized -- where there was vicilin, there was amyloid-specific dye. Vicilin amyloid aggregates built up in the storage vacuoles during seed maturation, and then rapidly disassembled during germination, suggesting their role is as a nutrient reservoir. They also found that vicilin amyloids survived intact in canned peas, resisted treatment with protein-digesting gastrointestinal enzymes, and were toxic to yeast and mammalian cells."Amyloids are highly stable protein structures that resist different treatments and can, in several cases, persist in the external environment for decades," Nizhnikov said. "Amyloid formation seems to be reasonable as evolutionary adaptation to provide for the long-term survival of plant seeds."
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Microbes
| 2,020 |
July 23, 2020
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https://www.sciencedaily.com/releases/2020/07/200723143733.htm
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Vikings had smallpox and may have helped spread the world's deadliest virus
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Scientists have discovered extinct strains of smallpox in the teeth of Viking skeletons -- proving for the first time that the killer disease plagued humanity for at least 1400 years.
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Smallpox spread from person to person via infectious droplets, killed around a third of sufferers and left another third permanently scarred or blind. Around 300 million people died from it in the 20th century alone before it was officially eradicated in 1980 through a global vaccination effort -- the first human disease to be wiped out.Now an international team of scientists have sequenced the genomes of newly discovered strains of the virus after it was extracted from the teeth of Viking skeletons from sites across northern Europe. The findings have been published in Professor Eske Willerslev, of St John's College, University of Cambridge, and director of The Lundbeck Foundation GeoGenetics Centre, University of Copenhagen, led the study.He said: "We discovered new strains of smallpox in the teeth of Viking skeletons and found their genetic structure is different to the modern smallpox virus eradicated in the 20th century. We already knew Vikings were moving around Europe and beyond, and we now know they had smallpox. People travelling around the world quickly spread Covid-19 and it is likely Vikings spread smallpox. Just back then, they travelled by ship rather than by plane."The 1400-year-old genetic information extracted from these skeletons is hugely significant because it teaches us about the evolutionary history of the variola virus that caused smallpox."Smallpox was eradicated throughout most of Europe and the United States by the beginning of the 20th century but remained endemic throughout Africa, Asia, and South America. The World Health Organisation launched an eradication programme in 1967 that included contact tracing and mass communication campaigns -- all public health techniques that countries have been using to control today's coronavirus pandemic. But it was the global roll out of a vaccine that ultimately enabled scientists to stop smallpox in its tracks.Historians believe smallpox may have existed since 10,000 BC but until now there was no scientific proof that the virus was present before the 17th century. It is not known how it first infected humans but, like Covid-19, it is believed to have come from animals.Professor Martin Sikora, one of the senior authors leading the study, from the Centre for GeoGenetics, University of Copenhagen, said: "The timeline of the emergence of smallpox has always been unclear but by sequencing the earliest-known strain of the killer virus, we have proved for the first time that smallpox existed during the Viking Age."While we don't know for sure if these strains of smallpox were fatal and caused the death of the Vikings we sampled, they certainly died with smallpox in their bloodstream for us to be able to detect it up to 1400 years later. It is also highly probable there were epidemics earlier than our findings that scientists have yet to discover DNA evidence of."The team of researchers found smallpox -- caused by the variola virus -- in 11 Viking-era burial sites in Denmark, Norway, Russia, and the UK. They also found it in multiple human remains from Öland, an island off the east coast of Sweden with a long history of trade. The team were able to reconstruct near-complete variola virus genomes for four of the samples.Dr Lasse Vinner, one of the first authors and a virologist from The Lundbeck Foundation GeoGenetics Centre, said: "Understanding the genetic structure of this virus will potentially help virologists understand the evolution of this and other viruses and add to the bank of knowledge that helps scientists fight emerging viral diseases."The early version of smallpox was genetically closer in the pox family tree to animal poxviruses such as camelpox and taterapox, from gerbils. It does not exactly resemble modern smallpox which show that virus evolved. We don't know how the disease manifested itself in the Viking Age -- it may have been different from those of the virulent modern strain which killed and disfigured hundreds of millions."Dr Terry Jones, one of the senior authors leading the study, a computational biologist based at the Institute of Virology at Charité -- Universitätsmedizin Berlin and the Centre for Pathogen Evolution at the University of Cambridge, said: "There are many mysteries around poxviruses. To find smallpox so genetically different in Vikings is truly remarkable. No one expected that these smallpox strains existed. It has long been believed that smallpox was in Western and Southern Europe regularly by 600 AD, around the beginning of our samples."We have proved that smallpox was also widespread in Northern Europe. Returning crusaders or other later events have been thought to have first brought smallpox to Europe, but such theories cannot be correct. While written accounts of disease are often ambiguous, our findings push the date of the confirmed existence of smallpox back by a thousand years."Dr Barbara Mühlemann, one of the first authors and a computational biologist, took part in the research during her PhD at the Centre for Pathogen Evolution at the University of Cambridge, and is now also based at the Institute of Virology at Charité, said: "The ancient strains of smallpox have a very different pattern of active and inactive genes compared to the modern virus. There are multiple ways viruses may diverge and mutate into milder or more dangerous strains. This is a significant insight into the steps the variola virus took in the course of its evolution."Dr Jones added: "Knowledge from the past can protect us in the present. When an animal or plant goes extinct, it isn't coming back. But mutations can re-occur or revert and viruses can mutate or spill over from the animal reservoir so there will always be another zoonosis."Zoonosis refers to an infectious disease outbreak caused by a pathogen jumping from a non-human animal to a human.The research is part of a long-term project sequencing 5000 ancient human genomes and their associated pathogens made possible thanks to a scientific collaboration between The Lundbeck Foundation, The Wellcome Trust, The Nordic Foundation, and Illumina Inc.Professor Willerslev concluded: "Smallpox was eradicated but another strain could spill over from the animal reservoir tomorrow. What we know in 2020 about viruses and pathogens that affect humans today, is just a small snapshot of what has plagued humans historically."
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Microbes
| 2,020 |
July 23, 2020
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https://www.sciencedaily.com/releases/2020/07/200723115234.htm
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How does cooperation evolve?
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In nature, organisms often support each other in order to gain an advantage. However, this kind of cooperation contradicts the theory of evolution proposed by Charles Darwin: Why would organisms invest valuable resources to help others? Instead, they should rather use them for themselves, in order to win the evolutionary competition with other species. A new study led by Prof. Dr. Christian Kost from the Department of Ecology at the Osnabrueck University now solved this puzzle. The results of the study were published in the scientific journal
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Interactions between two or more organisms, in which all partners involved gain an advantage, are ubiquitous in nature and have played a key role in the evolution of life on Earth. For example, root bacteria fix nitrogen from the atmosphere, thus making it available to plants. In return, the plant supplies its root bacteria with nutritious sugars. However, it is nevertheless costly for both interaction partners to support each other. For example, the provision of sugar requires energy, which is then not available to the plant anymore. From this results the risk of cheating interaction partners that consume the sugar without providing nitrogen in return.The research team led by Prof. Dr. Christian Kost used bacteria as a model system to study the evolution of mutual cooperation. At the beginning of the experiment, two bacterial strains could only grow when they provided each other with essential amino acids. Over the course of several generations, however, the initial exchange of metabolic byproducts developed into a real cooperation: both partners increased the production of the exchanged amino acids in order to benefit their respective partner. Even though the increased amino acid production enhanced growth when both partners were present, it was extremely costly when individual bacterial strains had to grow without their partner.The observed changes were caused by the fact that individual bacterial cells had assembled into multicellular clusters. In these cell groups, cooperative mutants were rewarded. The more resources they invested in the growth of other cells, the more nutrients they received in return from their partners."This kind of feedback represents a previously unknown mechanism, which promotes the evolution of cooperative interactions between two different organisms," says Prof. Dr. Christian Kost, leader of the study. Although the study was performed with bacteria in a test tube, the mechanism discovered can most likely explain the evolution of cooperation in many different ecological interactions.
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Microbes
| 2,020 |
July 22, 2020
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https://www.sciencedaily.com/releases/2020/07/200722134909.htm
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Antioxidant-rich powders from blueberry, persimmon waste could be good for gut microbiota
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Feeding the world's growing population in a sustainable way is no easy task. That's why scientists are exploring options for transforming fruit and vegetable byproducts -- such as peels or pulp discarded during processing -- into nutritious food ingredients and supplements. Now, researchers reporting in ACS'
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In recent years, fruit and vegetable powders have become popular as a way to add beneficial compounds, such as polyphenols and carotenoids (two types of antioxidants), to the diet, either by consuming the powders directly or as an ingredient in food products. However, in many cases these healthful compounds are present at similar or even higher levels in byproducts compared to those in other parts of the fruit or vegetable. Noelia Betoret, María José Gosalbes and colleagues wanted to obtain powders from persimmon and blueberry wastes, and then study how digestion could affect the release of antioxidants and other bioactive compounds. They also wanted to determine the effects of the digested powders on gut bacterial growth.The researchers obtained powders from persimmon peels and flower parts, and from the solids left behind after making blueberry juice. The type of powder, drying method, fiber content and type of fiber determined the release of antioxidants during a simulated digestion. For example, freeze-drying preserved more anthocyanins, but these were more easily degraded during digestion than those in air-dried samples. Then, the team added the powders to a fecal slurry and conducted a mock colonic fermentation, sequencing the bacteria present before and after fermentation. Incubation with the fruit powders resulted in an increase in several types of beneficial bacteria, and some bacteria grew better with one powder compared to the other. These findings indicate that persimmon and blueberry waste powders could be included in food formulations to boost the content of carotenoids and anthocyanins, which could have a positive impact on human health, the researchers say.
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Microbes
| 2,020 |
July 21, 2020
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https://www.sciencedaily.com/releases/2020/07/200721132737.htm
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Ultra-small, parasitic bacteria found in groundwater, moose -- and you
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Inside your mouth right now, there is a group of bacteria whose closest relatives can also be found in the belly of a moose, in dogs, cats, and dolphins, and in groundwater deep under the Earth's surface. In a stunning discovery, scientists have found that these organisms have adapted to these incredibly diverse environments -- without radically changing their genomes.
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The organisms are members of the TM7, or Sacchraribacteria, phylum. These are ultra-small, parasitic bacteria with small genomes that belong to a larger group called the Candidate Phyla Radiation (CPR). These CPR bacteria are mysterious "dark matter" that represent more than 25 percent of all bacterial diversity, yet we know very little about them since the vast majority remain uncultivated.In research first published as a pre-print in 2018, and now formally in the journal "It's the only bacteria we know that has hardly changed when they adapted to humans," said Dr. Jeffrey Scott McLean, a microbiologist and Associate Professor of Periodontics at the University of Washington School of Dentistry, and lead author of the paper.The TM7 bacteria were a complete mystery to scientists until Dr. Xuesong He, Associate Member of Staff at the Forsyth Institute and co-author of the paper, first isolated the bacterium TM7x, a member of CPR, in 2014. Since then, researchers have learned that CPR includes a huge number of different bacteria, all with tiny genomes. These bacteria need a host to survive and are unique in that they can't make their own amino acids and nucleotides, which are essential building blocks for life."I see this as a huge discovery," said Wenyuan Shi, CEO and Chief Scientific Officer at the Forsyth Institute and co-author on the paper. "This creature survives in both humans and groundwater, which indicates there are similarities that allow these bacteria to adapt to humans."Previous research by Dr. Batbileg Bor, Assistant Member of Staff at the Forsyth Institute and co-author of the paper, showed that TM7 can easily jump from one bacterial host to another. This could explain how they ended up in mammals, since mammals drink groundwater."The most likely reason we see a large diversity of these bacteria in humans, yet one group of bacteria remains nearly identical to those in groundwater, is that some groups were acquired in ancient mammal relatives and they expanded over time across mammals, whereas this one highly similar group more recently jumped directly into humans," McLean said.TM7 and other ultra-small, parasitic bacteria within CPR may play important roles in health and disease that we have yet to discover. Since they act as parasites -- living with and killing other bacteria -- TM7 could change the overall microbiome by modulating the abundance of bacteria, McLean said. Scientists are just scratching the surface of understanding how much our microbiome impacts our overall health.Another major contribution of this research has been developing a systematic way to name these newly discovered bacteria, setting the foundation for classifying other isolated strains in the future.The fact that humans acquired TM7 recently is a discovery that has broader implications for understanding our co-evolutionary pathways with the microbes that live on and within us."There are only a couple hundred genes that are different in these ultra-small bacteria between what lives deep in the subsurface environment and those that have become common bacteria in our mouths," McLean said. "That is a remarkable feat for bacteria missing so many genes."
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Microbes
| 2,020 |
July 20, 2020
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https://www.sciencedaily.com/releases/2020/07/200720164524.htm
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Advancing knowledge on archaea
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Bioinformatics and big data analyses can reap great rewards for biologists, but it takes a lot of work to generate the datasets necessary to begin. At the same time, researchers around the globe churn out datasets that could be useful to others but are not always widely shared.
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To foster scientific exchange and to advance discovery, biologists in the School of Arts & Sciences led by postdoc Stefan Schulze and professor Mecky Pohlschroder have launched the Archaeal Proteome Project (ArcPP), a web-based database to collect and make available datasets to further the work of all scientists interested in archaea, a domain of life composed of microorganisms that can dwell anywhere from deep-sea vents to the human gut."This is a very community-focused effort," says Schulze, who has worked as a postdoc in Pohlschroder's lab since 2017 and took the lead in developing the ArcPP platform, which is described in a recent Pohlschroder's lab studies the archaeon Haloferax volcanii as a model organism, a salt-loving species originally isolated from the Dead Sea. While the ArcPP launched with data from only this species, the researchers hope to rapidly grow it to encompass proteomic data -- a cataloging of the entire set of proteins contained in an organism -- from more archaeal species and even beyond, including other single-celled organisms, such as bacteria."The principle of the ArcPP can be seen as similar to the collaboration between medical specialists treating a patient," Schulze says. "Brain, heart, or kidney specialists all have expert knowledge in their respective fields, but for all of them a blood sample can help to interpret symptoms of a patient. Similar to that blood sample, modern proteomics, which can analyze the whole proteomes of an organism within a single experiment, provide information about various aspects of archaeal cell biology."Archaea are a relatively understudied group, but they play important ecological roles, are used for various biotechnological applications, and appear to be the prokaryotic ancestors of eukaryotes. Thus, the field is ripe for novel insights into their biochemistry and function.Recent advances have made it much simpler to generate the raw data needed to perform proteomics studies with an organism. "Now the bottleneck is how do you effectively analyze it, and what do you make out of this analysis," Pohlschroder says.That's where the ArcPP community comes in. "I might understand why certain proteins are expressed or modified on the cell surface because that's what we focus on in our lab," she says, "but our colleagues study other aspects of archaeal biology. By bringing together the community of scientists studying various aspects of archaeal proteomics, ArcPP can provide the research community with an abundance of easily accessible data and also has the expertise and perspectives needed to analyze the data in ways that will yield significant new insights into archaeal biology."To develop the ArcPP, the Penn biologists reached out to multiple laboratories around the world to contribute their proteomics datasets for H. volcanii. The data represented analyses of the microbes growing in a broad range of conditions, resulting in a collection that is a massive two terabytes in size."We were able to identify 72% of known proteins encoded in the H. volcanii proteome," Pohlschroder says. "By comparing different culture conditions, we were able to identify proteins that are always present, indicating that they are crucial for cell functions in a variety of environments. Interestingly, for at least 15% of these proteins the function is as of yet completely unknown, highlighting that our understanding of archaeal cell biology is still quite limited."Schulze put the platform to the test to see what new information could be gleaned. Together with other members of the group, he used the database to find that, contrary to what was previously believed about H. volcanii, it can express the enzyme urease, which breaks down the nitrogen compound urea, though only in the presence of glycerol as a carbon source. Follow-up experiments at the bench by collaborators from the University of Florida confirmed the finding, offering a proof-of-concept of the power of ArcPP."Expressing urease could be important in nitrogen cycling in the environment," Schulze says, "or even for biotechnology applications."Another powerful aspect of ArcPP is its utility for education. Bioinformatics is an invaluable skill for up-and-coming biologists, and analyses that can be done at the computer rather than the lab are a useful way to safely continue scientific discovery amid the COVID-19 pandemic. It's something that even the high school students that Pohlschroder invites into her lab through the program Penn LENS, short for Laboratory Experience in Natural Sciences, can experience in a hands-on format."What I think is fascinating about this project is that you can work with Haloferax volcanii, which is non-pathogenic and fairly easy to work with," Pohlschroder says, "and pair it with cutting-edge technology but do it in such a way that high school students are capable of making absolutely novel discoveries. It's something we are definitely thinking about using for the upcoming semester for undergraduates as well since they may not be able to come into the laboratory right away."A new study Schulze, Pohlschroder, doctoral student Heather Schiller, and colleagues, released as a pre-print to bioRxiv, prior to peer-review, also offers hints at how ArcPP might play a role in extending bench-based scientific discoveries. Many archaea, like bacteria, can form biofilms, which are microbial communities of adherent cells embedded in an extracellular polymeric matrix. H. volcanii can form biofilms either on solid surfaces or in liquid media. Schulze had noticed that, when H. volcanii forms a biofilm in liquid media contained in a petri dish, it can rapidly develop an intricate honeycomb pattern upon the removal of the petri dish lid.After some detective work to find out what is responsible for creating this formation, the researchers ruled out genes responsible for surface adhesion, light, oxygen, humidity, and other variables, and they now believe the driver to be a volatile compound in the air.While the group is planning further "wet lab" follow-up to determine whether other archaeal species and even certain bacteria do something similar, they also hope to lean on the ArcPP to better understand the mechanism of the honeycomb formation, as the included datasets contain proteomic information from microbes in biofilms as well as growing freely."I always see bioinformatics and lab work as a circle," Schulze says. "You may start with lab work, go to bioinformatics to probe into a finding, but you don't stop there. You should always go back to the lab -- and then back around -- to confirm and extend your findings."With ArcPP, these biologists are hoping to extend that circle, bringing more researchers -- and young people with scientific aspirations -- into the fold."We are eager to work together with more laboratories in order to extend our analyses to other archaeal species or even bacteria, harvesting the synergistic effects of a broad scientific community," says Pohlschroder.
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Microbes
| 2,020 |
July 20, 2020
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https://www.sciencedaily.com/releases/2020/07/200720164522.htm
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Better wastewater treatment? It's a wrap
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A shield of graphene helps particles destroy antibiotic-resistant bacteria and free-floating antibiotic resistance genes in wastewater treatment plants.
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Think of the new strategy developed at Rice University as "wrap, trap and zap."The labs of Rice environmental scientist Pedro Alvarez and Yalei Zhang, a professor of environmental engineering at Tongji University, Shanghai, introduced microspheres wrapped in graphene oxide in the Elsevier journal Alvarez and his partners in the Rice-based Nanosystems Engineering Research Center for Nanotechnology-Enabled Water Treatment (NEWT) have worked toward quenching antibiotic-resistant "superbugs" since first finding them in wastewater treatment plants in 2013."Superbugs are known to breed in wastewater treatment plants and release extracellular antibiotic resistance genes (ARGs) when they are killed as the effluent is disinfected," Alvarez said. "These ARGs are then discharged and may transform indigenous bacteria in the receiving environment, which become resistome reservoirs."Our innovation would minimize the discharge of extracellular ARGs, and thus mitigate dissemination of antibiotic resistance from wastewater treatment plants," he said.The Rice lab showed its spheres -- cores of bismuth, oxygen and carbon wrapped with nitrogen-doped graphene oxide -- inactivated multidrug-resistant Escherichia coli bacteria and degraded plasmid-encoded antibiotic-resistant genes in secondary wastewater effluent.The graphene-wrapped spheres kill nasties in effluent by producing three times the amount of reactive oxygen species (ROS) as compared to the spheres alone.The spheres themselves are photocatalysts that produce ROS when exposed to light. Lab tests showed that wrapping the spheres minimized the ability of ROS scavengers to curtail their ability to disinfect the solution.The researchers said nitrogen-doping the shells increases their ability to capture bacteria, giving the catalytic spheres more time to kill them. The enhanced particles then immediately capture and degrade the resistant genes released by the dead bacteria before they contaminate the effluent."Wrapping improved bacterial affinity for the microspheres through enhanced hydrophobic interaction between the bacterial surface and the shell," said co-lead author Pingfeng Yu, a postdoctoral research associate at Rice's Brown School of Engineering. "This mitigated ROS dilution and scavenging by background constituents and facilitated immediate capture and degradation of the released ARGs."Because the wrapped spheres are large enough to be filtered out of the disinfected effluent, they can be reused, Yu said. Tests showed the photocatalytic activity of the spheres was relatively stable, with no significant decrease in activity after 10 cycles. That was significantly better than the cycle lifetime of the same spheres minus the wrap.
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Microbes
| 2,020 |
July 20, 2020
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https://www.sciencedaily.com/releases/2020/07/200720102054.htm
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A new species of darkling beetle larvae that degrade plastic
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There floats an enormous plastic garbage island in the North Pacific that is seven times the size of the Korean Peninsula. The island, called the Great Pacific Garbage Patch, is the result of 13 million tons of plastic that flow into the ocean annually from the 20,000 units of plastic consumed per second around the world. Plastic takes decades to hundreds of years to decompose naturally with plastic bags taking 10 to 20 years, nylon products or disposable straws 30 to 40 years, and plastic water bottles -- commonly used once then thrown away -500 years to decompose. This problem of plastic, which has been labeled a human disaster, has been recently proven to be decomposable by beetles common in Korea.
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A joint research team consisting of Professor Hyung Joon Cha and a doctoral student Seongwook Woo of the Department of Chemical Engineering at POSTECH with Professor Intek Song of Andong National University has uncovered for the first time that the larvae of the beetle in the order Coleoptera (Plesiophthophthalmus davidis) can decompose polystyrene, a material that is tricky to decompose.By 2017, 8.3 billion tons of plastic waste were produced across the globe, of which less than 9 percent were recycled. Polystyrene, which accounts for about 6% of total plastic production, is known to be difficult to decompose due to its unique molecular structure.The research team found that the larvae of a darkling beetle indigenous to East Asia including the Korean peninsula can consume polystyrene and reduce both its mass and molecular weight. The team also confirmed that the isolated gut flora could oxidize and change the surface property of the polystyrene film.Meanwhile, the research team isolated and identified Serratia from the intestinal tract of P. davidis larvae. When polystyrene was fed to the larvae for two weeks, the proportion of Serratia in the gut flora increased by six fold, accounting for 33 percent of the overall gut flora. Moreover, it was found that the gut flora of this larvae consisted of a very simple group of bacterial species (less than six) unlike the gut flora of other conventional polystyrene-degrading insects.The unique diet of the darkling beetle larvae that was uncovered in this study presents the possibility that polystyrene can be broken down by other insects that feed on rotten wood. In addition, the development of an effective polystyrene-decomposing flora using the bacterial strains found in the simple gut flora of P. davidis is highly anticipated.The study is also noteworthy in that the paper's first author, Seongwook Woo, who has been interested in insects since childhood and wished to make the world a better place through them, sought out Professor Cha as soon as he entered POSTECH and focused on research under his supervision over the years.As the corresponding author of the paper, Professor Cha commented, "We have discovered a new insect species that lives in East Asia -- including Korea -- that can biodegrade plastic through the gut flora of its larvae." He concluded, "If we use the plastic-degrading bacterial strain isolated in this study and replicate the simple gut floral composition of P. davidis, there is the chance that we could completely biodegrade polystyrene, which has been difficult to completely decompose, to ultimately contribute to solving the plastic waste problem that we face."These research findings were recently published in the online edition of
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Microbes
| 2,020 |
July 17, 2020
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https://www.sciencedaily.com/releases/2020/07/200717133240.htm
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SARS-CoV-2 is not transmitted by mosquitoes, study shows
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A new study by Kansas State University researchers is the first to confirm that SARS-CoV-2 cannot be transmitted to people by mosquitoes.
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Stephen Higgs, associate vice president for research and director of the university's Biosecurity Research Institute, or BRI, together with colleagues from the BRI and the College of Veterinary Medicine had the findings published July 17 by The article, "SARS-CoV-2 failure to infect or replicate in mosquitoes: an extreme challenge," details the study's findings, which provide the first experimental investigation on the capacity of SARS-CoV-2, the virus that causes COVID-19 disease, to infect and be transmitted by mosquitoes."While the World Health Organization has definitively stated that mosquitoes cannot transmit the virus, our study is the first to provide conclusive data supporting the theory," said Higgs, Peine professor of biosecurity and university distinguished professor of diagnostic medicine and pathobiology.The study, which was done at the BRI, a biosecurity level-3 facility, ultimately found that the virus is unable to replicate in three common and widely distributed species of mosquitoes -- Aedes aegypti, Aedes albopictus and Culex quinquefasciatus -- and therefore cannot be transmitted to humans."I am proud of the work we are doing at K-State to learn as much as we can about this and other dangerous pathogens," said Higgs. "This work was possible because of the unique capabilities of the BRI and the dedicated BRI and institutional staff."Colleagues involved with the study include Yan-Jang Huang, research assistant professor of diagnostic medicine and pathobiology; Dana Vanlandingham, professor of diagnostic medicine and pathobiology; Ashley Bilyeu and Haelea Sharp, research assistants in diagnostic medicine and pathobiology; and Susan Hettenbach, research assistant at the BRI.Researchers at the BRI have completed four additional studies on COVID-19 since March and this is the first peer-reviewed publication based on SARS-CoV-2 experiments wholly conducted at K-State.Research at the Biosecurity Research Institute has been ongoing with other animal pathogens that can be transmitted from animals to people, including Rift Valley fever and Japanese encephalitis, as well as diseases that could devastate America's food supply, such as African swine fever and classical swine fever. The research was in part supported by the National Bio and Agro-Defense Facility Transition Fund provided by the state of Kansas."We have remarkable talent and capabilities working within our research and training facility at the BRI," said Peter Dorhout, K-State vice president for research. "The BRI is one of the critical anchor facilities in the North Campus Corridor, which serves as our growing research and development space for private sector and government agency partnerships with K-State."
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Microbes
| 2,020 |
July 17, 2020
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https://www.sciencedaily.com/releases/2020/07/200717120154.htm
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Turmeric could have antiviral properties
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Curcumin, a natural compound found in the spice turmeric, could help eliminate certain viruses, research has found.
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A study published in the Infection with TGEV causes a disease called transmissible gastroenteritis in piglets, which is characterised by diarrhea, severe dehydration and death. TGEV is highly infectious and is invariably fatal in piglets younger than two weeks, thus posing a major threat to the global swine industry. There are currently no approved treatments for alpha-coronaviruses and although there is a vaccine for TGEV, it is not effective in preventing the spread of the virus.To determine the potential antiviral properties of curcumin, the research team treated experimental cells with various concentrations of the compound, before attempting to infect them with TGEV. They found that higher concentrations of curcumin reduced the number of virus particles in the cell culture.The research suggests that curcumin affects TGEV in a number of ways: by directly killing the virus before it is able to infect the cell, by integrating with the viral envelope to 'inactivate' the virus, and by altering the metabolism of cells to prevent viral entry. "Curcumin has a significant inhibitory effect on TGEV adsorption step and a certain direct inactivation effect, suggesting that curcumin has great potential in the prevention of TGEV infection," said Dr Lilan Xie, lead author of the study and researcher at the Wuhan Institute of Bioengineering.Curcumin has been shown to inhibit the replication of some types of virus, including dengue virus, hepatitis B and Zika virus. The compound has also been found to have a number of significant biological effects, including antitumor, anti-inflammatory and antibacterial activities. Curcumin was chosen for this research due to having low side effects according to Dr Xie. They said: "There are great difficulties in the prevention and control of viral diseases, especially when there are no effective vaccines. Traditional Chinese medicine and its active ingredients, are ideal screening libraries for antiviral drugs because of their advantages, such as convenient acquisition and low side effects."The researchers now hope to continue their research in vivo, using an animal model to assess whether the inhibiting properties of curcumin would be seen in a more complex system. "Further studies will be required, to evaluate the inhibitory effect in vivo and explore the potential mechanisms of curcumin against TGEV, which will lay a foundation for the comprehensive understanding of the antiviral mechanisms and application of curcumin" said Dr Xie.
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Microbes
| 2,020 |
July 16, 2020
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https://www.sciencedaily.com/releases/2020/07/200716120658.htm
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Beautyberry leaf extract restores drug's power to fight 'superbug'
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Scientists discovered a compound in the leaves of a common shrub, the American beautyberry, that boosts an antibiotic's activity against antibiotic-resistant staph bacteria. Laboratory experiments showed that the plant compound works in combination with oxacillin to knock down the resistance to the drug of methicillin-resistant Staphylococcus aureus, or MRSA.
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The American Chemical Society's Infectious Diseases published the finding, led by scientists at Emory University and the University of Notre Dame.The American beautyberry, or "We decided to investigate the chemical properties of the American beautyberry because it was an important medicinal plant for Native Americans," says Cassandra Quave, co-senior author of the study and an assistant professor in Emory University's Center for the Study of Human Health and Emory School of Medicine's Department of Dermatology. Quave is also a member of the Emory Antibiotic Resistance Center and a leader in the field of medical ethnobotany, studying how indigenous people incorporate plants in healing practices to uncover promising candidates for new drugs.Micah Dettweiler, a recent Emory graduate and a staff member of the Quave lab, is first author of the study. Christian Melander, professor of chemistry at Notre Dame, is co-senior author.The Alabama, Choctaw, Creek, Koasati, Seminole and other Native American tribes relied on the American beautyberry for various medicinal purposes. Leaves and other parts of the plant were boiled for use in sweat baths to treat malarial fevers and rheumatism. The boiled roots were made into treatments for dizziness, stomachaches and urine retention, while bark from the stems and roots were made into concoctions for itchy skin.Previous research found that extracts from the leaves of the beautyberry deter mosquitoes and ticks. And a prior study by Quave and colleagues found that extracts from the leaves inhibit growth of the bacterium that causes acne. For this study, the researchers focused on testing extracts collected from the leaves for efficacy against MRSA."Even a single plant tissue can contain hundreds of unique molecules," Quave says. "It's a painstaking process to chemically separate them out, then test and retest until you find one that's effective."The researchers identified a compound from the leaves that slightly inhibited the growth of MRSA. The compound belongs to a group of chemicals known as clerodane diterpenoids, some of which are used by plants to repel predators.Since the compound only modestly inhibited MRSA, the researchers tried it in combination with beta-lactam antibiotics."Beta-lactam antibiotics are some of the safest and least toxic that are currently available in the antibiotic arsenal," Quave says. "Unfortunately, MRSA has developed resistance to them."Laboratory tests showed that the beautyberry leaf compound synergizes with the beta-lactam antibiotic oxacillin to knock down MRSA's resistance to the drug.The next step is to test the combination of the beautyberry leaf extract and oxacillin as a therapy in animal models. If those results prove effective against MRSA infections, the researchers will synthesize the plant compound in the lab and tweak its chemical structure to try to further enhance its efficacy as a combination therapy with oxacillin."We need to keep filling the drug-discovery pipeline with innovative solutions, including potential combination therapies, to address the ongoing and growing problem of antibiotic resistance," Quave says.Each year in the U.S., at least 2.8 million people get an antibiotic-resistant infection and more than 35,000 people die, according to the Centers for Disease Control and Prevention."Even in the midst of the COVID-19, we can't forget about the issue of antibiotic resistance," Quave says. She notes that many COVID-19 patients are receiving antibiotics to deal with secondary infections brought on by their weakened conditions, raising concerns about a later surge in antibiotic-resistant infections.
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Microbes
| 2,020 |
July 16, 2020
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https://www.sciencedaily.com/releases/2020/07/200716101543.htm
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When many act as one, data-driven models can reveal key behaviors
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Biology is rife with examples of collective behavior, from flocks of birds and colonies of bacteria to schools of fish and mobs of people. In a study with implications from oncology to ecology, researchers from Rice University and the University of Georgia have shown that data science can unlock subtle clues about the individual origins of collective behavior.
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When a group of individuals move in synch, they can create patterns -- like the flocking of birds or "the wave" in a sports stadium -- that no single individual could make. While these emergent behaviors can be fascinating, it can be difficult for scientists to zero in on the individual actions that bring them about."You see emergent behaviors by looking at the group rather than the individual," said Rice bioengineer Oleg Igoshin, a theoretical biophysicist who has spent almost 20 years studying emergent behavior in cells -- be they cooperative bacteria, cancer cells or others.In a study published online this week in the American Society for Microbiology journal To illustrate both the difficulty and the importance of understanding these individual contributions to the collective group, Igoshin uses the example of metastatic cancer, where a group of cells with a particular mutation are moving toward the surface of a tumor so they can break away and form a new tumor elsewhere."Most of these cells fail to escape the original tumor, and the question is, what determines which ones will succeed?" asked Igoshin, a professor of bioengineering and senior scientist at Rice's Center for Theoretical Biological Physics. "What property is a signal for emergence? Is it how fast they move? Is it how long they move before changing direction? Perhaps it's how frequently they stop. Or it could be a combination of several signals, each of which is too weak to bring about emergence on its own but which act to reinforce one another."As a group, the potentially metastatic cancer cells share some key traits and abilities, but as individuals, their performance can vary. And in a large population of cells, these performance differences can be as stark as those between Olympic athletes and couch potatoes. Above all, it is this natural variation in individual performance, or heterogeneity, that makes it so difficult to zero in on individual behaviors that contribute to emergent behaviors, Igoshin said."Even for cells in a genetically homogeneous tumor, if you look at individuals there will be a distribution, some heterogeneity in performance that arises from some individuals performing 50% above average and others 50% below average," he said. "So the question is, 'With all of this background noise, how can we find the weak trends or signals associated with emergence?'"Igoshin said the new method incorporates data science to overcome some weaknesses of traditional modeling. By populating their models with experimental data about the movements of individual cells, Igoshin said he and Zhang, who received his Ph.D. from Rice in May, simplified the search for individual behaviors that influence group behaviors.To demonstrate the technique, they partnered with Lawrence Shimkets, whose lab at the University of Georgia (UGA) has spent years compiling data about the individual and group behaviors of the cooperative soil bacterium Myxococcus xanthus."They're predatory microbes, but they are smaller than many of the things they eat," Igoshin said of M. xanthus. "They work together, kind of like a wolf pack, to surround their prey and make the chemicals that will kill it and digest it outside of their bodies, turning it into molecules that are small enough for them to take in."During times of stress, like when food is running short, M. xanthus exhibit a form of emergent behavior that has been studied for decades. Like lines of cars flowing into a city at rush hour, they stream together to form densely packed mounds that are large enough to see with the naked eye. Mound formation is an early step in the process of forming rugged long-lived spores that can reestablish the colony when conditions improve.In a previous study, UGA's Chris Cotter, a co-author of the new study and a graduate student in Shimkets' group, tracked individual behaviors of wild-type cells and collaborated with Igoshin to develop a data-driven model that uncovers the cellular behaviors that are key to aggregation. In the new study, Cotter and Zhe Lyu, a former UGA postdoctoral researcher now at Baylor College of Medicine in Houston, collected mound-forming data from mixtures of three strains of M. xanthus: a naturally occurring wild type and two mutants. On their own, the mutants were incapable of forming mounds. But when a significant number of wild-type cells were mixed with the mutants, they were "rescued," meaning they integrated with the collective and took part in mound-building."One of the mutants is fully rescued while the other is only partially rescued, and the goal is to understand how rescue works," Igoshin said. "When we applied the methodology, we saw several things that were unexpected. For example, for the mutant that's fully rescued, you might expect that it behaves normally, meaning that all its properties -- its speeds, its behaviors -- will be exactly the same as the wild type. But that's not the case. What we found was that the mutant performed better than normal in some respects and worse in others. And those compensated for one another so that it appeared to be behaving normally."Emergent behaviors in M. xanthus are well-studied, classic examples. In addition to showing that their method can unlock some of the mysteries of M. xanthus' behavior, Igoshin said the new study indicates the method can be used to investigate other emergent behaviors, including those implicated in diseases and birth defects."All we need is data on individuals and data on the emergent behavior, and we can apply this method to ask whether a specific type of individual behavior contributes to the collective, emergent behavior," he said. "It doesn't matter what kind of cell it is, and I think it could even be applied to study animals in ecological models. For instance, ecologists studying migration of a species into a new territory often collect GPS-tracking data. In principle, with enough data on individual behavior, you should be able to apply this approach to study collective, herd-level behaviors."The research was supported by the National Science Foundation (DMS-1903275, IOS-1856742, MCB-1411891, PHY-1427654) and the Welch Foundation (C-1995).
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Microbes
| 2,020 |
July 15, 2020
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https://www.sciencedaily.com/releases/2020/07/200715142337.htm
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Bacteria with a metal diet discovered in dirty glassware
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Caltech microbiologists have discovered bacteria that feed on manganese and use the metal as their source of calories. Such microbes were predicted to exist over a century ago, but none had been found or described until now.
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"These are the first bacteria found to use manganese as their source of fuel," says Jared Leadbetter, professor of environmental microbiology at Caltech who, in collaboration with postdoctoral scholar Hang Yu, describes the findings in the July 16 issue of the journal The study also reveals that the bacteria can use manganese to convert carbon dioxide into biomass, a process called chemosynthesis. Previously, researchers knew of bacteria and fungi that could oxidize manganese, or strip it of electrons, but they had only speculated that yet-to-be-identified microbes might be able to harness the process to drive growth.Leadbetter found the bacteria serendipitously after performing unrelated experiments using a light, chalk-like form of manganese. He had left a glass jar soiled with the substance to soak in tap water in his Caltech office sink before departing for several months to work off campus. When he returned, the jar was coated with a dark material."I thought, 'What is that?'" he explains. "I started to wonder if long-sought-after microbes might be responsible, so we systematically performed tests to figure that out."The black coating was in fact oxidized manganese generated by newfound bacteria that had likely come from the tap water itself. "There is evidence that relatives of these creatures reside in groundwater, and a portion of Pasadena's drinking water is pumped from local aquifers," he says.Manganese is one of the most abundant elements on the surface of the earth. Manganese oxides take the form of a dark, clumpy substance and are common in nature; they have been found in subsurface deposits and can also form in water-distribution systems."There is a whole set of environmental engineering literature on drinking-water-distribution systems getting clogged by manganese oxides," says Leadbetter. "But how and for what reason such material is generated there has remained an enigma. Clearly, many scientists have considered that bacteria using manganese for energy might be responsible, but evidence supporting this idea was not available until now."The finding helps researchers better understand the geochemistry of groundwater. It is known that bacteria can degrade pollutants in groundwater, a process called bioremediation. When doing this, several key organisms will "reduce" manganese oxide, which means they donate electrons to it, in a manner similar to how humans use oxygen in the air. Scientists have wondered where the manganese oxide comes from in the first place."The bacteria we have discovered can produce it, thus they enjoy a lifestyle that also serves to supply the other microbes with what they need to perform reactions that we consider to be beneficial and desirable," says Leadbetter.The research findings also have possible relevance to understanding manganese nodules that dot much of the seafloor. These round metallic balls, which can be as large as grapefruit, were known to marine researchers as early as the cruises of the HMS Challenger in the 1870s. Since then, such nodules have been found to line the bottom of many of Earth's oceans. In recent years, mining companies have been making plans to harvest and exploit these nodules, because rare metals are often found concentrated within them.But little is understood about how the nodules form in the first place. Yu and Leadbetter now wonder if microbes similar to what they have found in freshwater might play a role and they plan to further investigate the mystery. "This underscores the need to better understand marine manganese nodules before they are decimated by mining," says Yu."This discovery from Jared and Hang fills a major intellectual gap in our understanding of Earth's elemental cycles, and adds to the diverse ways in which manganese, an abstruse but common transition metal, has shaped the evolution of life on our planet," says Woodward Fischer, professor of geobiology at Caltech, who was not involved with the study.
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Microbes
| 2,020 |
July 15, 2020
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https://www.sciencedaily.com/releases/2020/07/200715123122.htm
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Bed bugs modify microbiome of homes they infest
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Homes infested by bed bugs appear to have different bacterial communities -- often referred to as microbiomes -- than homes without bed bugs, according to a first-of-its-kind study from North Carolina State University. In addition, once bed bug infestations were eradicated, home microbiomes became more similar to those in homes that never had bed bugs. The findings could be an important step in lifting the veil on the factors involved in indoor environmental quality and how to improve it.
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Microbes can affect indoor air quality. So NC State entomologists Coby Schal and Madhavi Kakumanu wanted to learn more about the microbiomes of bed bugs, whether bed bugs can shape the microbial community in homes they infest, and whether eliminating bed bugs changes the microbiome of homes that were once infested.The study, held in an apartment complex in Raleigh, compared the microbiomes of bed bugs with the microbiomes in the household dust of infested homes as well as the microbiomes in apartments that had no bed bugs. Nineteen infested homes were studied over the course of four months; seven were treated with heat to eliminate bed bugs after the initial sample was taken, while 12 infested homes were treated after one month. These homes were compared with 11 homes that had no bed bugs.The results showed similarities between the microbiomes of bed bugs and the dust-associated microbiomes of infested homes, mostly through the presence of Wolbachia, a symbiotic bacterium that comprises the majority of the bacterial abundance in bed bugs. Bed bug and infested home microbiomes differed significantly from the microbial communities of uninfested homes."There is a link between the microbiome of bed bugs and the microbiome of household dust in bed bug infested homes," said Schal, the Blanton J. Whitmire Distinguished Professor of Entomology at NC State and co-corresponding author of the paper. "No previous study has reported the impact of chronic pest infestations on indoor microbial diversity."The study also showed that, after bed bugs were eliminated, infested home microbiomes gradually became more like those in homes without bed bugs."The elimination of the bed bugs resulted in gradual shifts in the home microbial communities toward those of uninfested homes," Kakumanu, an NC State research scholar in Schal's lab and co-corresponding author of the study, said. "This paper is the first experimental demonstration that eliminating an indoor pest alters the indoor microbiome toward that of uninfested homes.""Bed bug infestations are problematic in many homes in both developed and developing countries," Schal said. "There is a critical need to investigate infestations from the perspective of indoor environmental quality, and this paper represents a first step toward this end."
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Microbes
| 2,020 |
July 15, 2020
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https://www.sciencedaily.com/releases/2020/07/200715142400.htm
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High-fat diet with antibiotic use linked to gut inflammation
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UC Davis researchers have found that combining a Western-style high-fat diet with antibiotic use significantly increases the risk of developing pre-inflammatory bowel disease (pre-IBD). The study, published July 14 in
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Irritable bowel syndrome (IBS) affects approximately 11% of people worldwide. It is characterized by recurring episodes of abdominal pain, bloating and changes in bowel habits. IBS patients with mucosal inflammation and changes in the gut's microbial composition are considered pre-IBD.The study included 43 healthy adults and 49 adult patients diagnosed with IBS. The researchers measured fecal calprotectin, a biomarker for intestinal inflammation, of participants. Elevated levels of fecal calprotectin indicated a pre-IBD condition. The study identified 19 patients with IBS as pre-IBD.The researchers found that all participants who consumed high-fat diet and used antibiotics were at 8.6 times higher risk for having pre-IBD than those on low-fat diet and no recent history of antibiotic use. Participants with the highest fat consumption were about 2.8 times more likely to have pre-IBD than those with the lowest fat intake. A history of recent antibiotic usage alone was associated with 3.9 times higher likelihood of having pre-IBD."Our study found that a history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD," said Andreas Bäumler, professor of medical microbiology and immunology and lead author on the study. "Until now, we didn't appreciate how different environmental risk factors can synergize to drive the disease."Using mouse models, the study also tested the effect of high-fat diet and antibiotics use on the cells in the intestinal lining. It found that high-fat diet and antibiotics cooperate to disrupt the work of the cell's mitochondria, shutting its ability to burn oxygen. This disruption causes reduction in cell's oxygen consumption and leads to oxygen leakage into the gut.The body's beneficial bacteria thrive in environments lacking oxygen such as the large intestine. Higher oxygen levels in the gut promote bacterial imbalances and inflammation. With the disruption in the gut environment, a vicious cycle of replacing the good bacteria with potentially harmful proinflammatory microbes that are more oxygen tolerant begins. This in turn leads to mucosal inflammation linked to pre-IBD conditions.The study also identified 5-aminosalicylate (mesalazine), a drug that restarts the energy factories in the intestinal lining, as a potential treatment for pre-IBD."The best approach to a healthy gut is to get rid of the preferred sustenance of harmful microbes," Lee said. "Our study emphasized the importance of avoiding high fat food and abuse of antibiotics to avoid gut inflammation."Co-authors on this study are Stephanie Cevallos, Mariana Byndloss, Connor Tiffany, Erin Olsan, Brian Butler, Briana Young, Andrew Rogers, Henry Nguyen, Kyongchol Kim, Sang-Woon Choi, Eunsoo Bae, Je Hee Lee, Ui-Gi Min and Duk-Chul Lee.This work was supported by the National Research Foundation of Korea grant(NRF-2017R1C1B5016190), USDA/NIFA award 2015-67015-22930 and by the Public Health Service grants AI044170, AI096528, AI112445, AI112949, AI060555 and 5TL1R001861.
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Microbes
| 2,020 |
July 13, 2020
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https://www.sciencedaily.com/releases/2020/07/200713125459.htm
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'Lab in a suitcase' could hold the key to safer water and sanitation for millions
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A portable testing lab that fits into a suitcase is being hailed as the key to tackling one of the world's biggest dangers to health.
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Experts from Newcastle University UK, have been working with the Addis Ababa Water and Sewerage Authority (AAWSA), Addis Ababa University (AAU) and the International Water Management Institute (IWMI) to ensure waterborne hazards can be identified in a quicker, easier and ultimately cheaper way, anywhere in the world.Using smaller and less expensive versions of the same type of specialist equipment found in state-of-the-art microbiology laboratories in the UK, the new suitcase lab -- believed to be a world first -- enables screening of millions of bacteria in a single water sample, instead of running many tests in parallel to look for different pathogens.Genetic analysis can bring to light numerous hazards potentially present in water, but such analysis is currently carried out in a laboratory, using large and expensive machines. These facilities are often not available in developing countries, and the process of sending samples from the affected country to the UK for detailed analysis can take more than a month.The portable lab means scientists can go direct to the location where a waterborne disease is thought to be present and screen a water sample for genetic material -- with results available within a day or two.The data can be used for measuring the effectiveness of wastewater treatment, faecal pollution source tracking and the identification of waterborne hazards in surface and groundwater. The rapid data generation gives public health officials more opportunity to quickly identify and deal with local hazards, potentially saving countless lives.After initial on-site testing on samples collected at Birtley sewage treatment plant in North East England, the suitcase lab was used to carry out water quality screening in the Akaki River catchment near Addis Ababa, Ethiopia. These achievements have just been published in the journal Dr David Werner, Professor in Environmental Systems Modelling, Newcastle University, explains: "By taking advantage of innovative technologies to make it easier and faster to carry out on-site water quality assessments, and with our Ethiopian colleagues, we have demonstrated a way to study genetic material with affordable resources almost anywhere in the world."With our portable laboratory we successfully screened millions of bacteria in Akaki River water samples and discovered a high prevalence of Arcobacter butzleri, a still poorly understood waterborne hazard that can cause watery diarrhea. Unfortunately, diarrhoea is still a leading cause of death among children under the age of five."Government advice to "wash your hands frequently" exemplifies the importance of safe water and sanitation for hygiene and public health. But according to the United Nations, six in 10 people lack access to safely managed sanitation facilities and three in 10 people in the world lack access to safely managed drinking water services.As well as reducing the time required to measure water quality, the project aims to enable the independent use of the tools by researchers and water systems engineers in Ethiopia. Dr Alemseged Tamiru Haile from the IWMI is confident that the scientific break-through will make a difference in Ethiopia."Our collaboration with Newcastle University in terms of carrying out the field work and analysis provided an opportunity for the hands-on training of 13 junior experts in Ethiopia at AAWSA facilities," he says. "One AAWSA staff member then visited Newcastle to receive intensive training in water quality monitoring with the portable laboratory. Academics from AAU can now integrate the novel approach into their curriculum. The equipment items we have assembled in the portable laboratory are affordable for AAU and AAWSA."AAWSA is constructing more sewage treatment plants in Addis Ababa, and the team will continue their monitoring in the Akaki catchment to provide evidence for the benefits of these investments in public health.Dr Kishor Acharya is the early career scientist at Newcastle University who has led the development of the portable molecular toolbox. He has delivered training workshops in portable metagenomics to junior academics and laboratory technicians from research institutions, NGOs, and government agencies in Tanzania, Thailand, Malaysia, Nepal, India and Ethiopia.Dr Acharya, who is originally from Nepal, says that the portable lab kit could easily be used in many different contexts to screen for dangerous pathogens. "I want to demonstrate the applicability of the mobile toolkit and the protocols we've developed for microbial hazard surveying to other disciplines," he explains. "In the future, this kit could potentially be used as a way to assure food and drink safety, efficient health services, productive agriculture and beyond."
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Microbes
| 2,020 |
July 9, 2020
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https://www.sciencedaily.com/releases/2020/07/200709172852.htm
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Neonatal exposure to antigens of commensal bacteria promotes broader immune repertoire
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University of Alabama at Birmingham researchers have added fresh evidence that early exposure to vaccine-, bacterial- or microbiota-derived antigens has a dramatic effect on the diversity of antibodies an adult mammal will have to fight future infections by pathogens. This antibody diversity is called the clonal repertoire -- basically different single cells with distinct antibody potential that can multiply into a large clone of cells, all producing that distinct antibody.
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In a mouse study published in the journal The UAB researchers, led by first author J. Stewart New, Ph.D., and co-senior authors John Kearney, Ph.D., and R. Glenn King, Ph.D., UAB Department of Microbiology, looked at a subset of B-1 B cells that react to N-acetyl-D-glucosamine-containing Lancefield Group A carbohydrate, or GAC, a cell wall polysaccharide of the bacterial pathogen Streptococcus pyogenes.They asked the question, how much will clonal diversity differ in mice grown under sterile germ-free conditions, versus mice with a normal gut microbiota from birth, or mice with a normal microbiota that are also vaccinated as neonates with GAC-bearing S. pyogenes. To answer, they sequenced the immunoglobulin heavy chain variable region, or IGHV region, for single B cells labeled with GAC. Single-cell sequencing has exploded in the past decade as a powerful research tool that takes biology to a new depth of understanding.New, Kearney, King and colleagues found that environmental antigen-dependent selection events play a significant role to shape the GAC-reactive B-1 B cell clonal repertoire. New is a postdoctoral fellow, Kearney is a professor, and King is assistant professor of microbiology in the UAB School of Medicine.In general, germ-free mice had a low IGHV clonal diversity, while both conventional mice and neonatal-vaccination mice had high clonal diversities. However, the conventional and neonatal-vaccination mice differed. Both showed that the establishment of IGHV region 6-3 GAC-reactive B cell clonal dominance was microbiota-dependent; but in addition, the neonatal immunization with S. pyogenes expanded the typically minor IGHV region 7-3 GAC-reactive clonotypes, compared to those clonotypes in the conventional mice.The researchers found that colonization of adult germ-free mice promoted N-acetyl-D-glucosamine-reactive B-1 B cell development and led to clonally related immunoglobulin A-positive plasma cells in the small intestine. Plasma cells differentiate from B cells, and they are the ones that produce antibody. Immunoglobulin A secretion in the gut is beneficial because it helps constrain the composition and inflammatory activity of the normal microbiota in the small intestine.Kearney says that understanding how exposure to microbial antigens in early life determines the clonality and ensuing antibody responses of the B-1 B cell repertoire has implications for vaccination approaches and schedules.B-1 B cells also are known to produce natural immunoglobulin M. Deficiencies of immunoglobulin M have been associated with increased rates of autoimmunity and allergic diseases. The dramatic effect of early exposure to vaccine or bacteria for clonal diversity seen in the current research, Kearney said, "may provide an alternative mechanistic explanation for the influence of environmental antigens on the allergic and autoimmune disease susceptibility, which is often discussed in context of the hygiene hypothesis."The hygiene hypothesis suggests that a reduction in infections in Western countries -- due to better hygiene -- has led to an increase in autoimmune and allergic diseases.Support came from National Institutes of Health grants AI14782, AI100005, AI120500, A1007051, DK082277 and GM008861.
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Microbes
| 2,020 |
July 9, 2020
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https://www.sciencedaily.com/releases/2020/07/200709172837.htm
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Salmonella biofilm protein causes autoimmune responses -- Possible link with Alzheimer's
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Scientists from the Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) at the University of Saskatchewan (USask) and Temple University (Philadelphia, U.S.) have demonstrated that a Salmonella biofilm protein can cause autoimmune responses and arthritis in animals.
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Salmonella was previously thought to only form biofilms in the environment, such as on food processing surfaces. Biofilms are dense collections of bacteria that stick together on surfaces to protect the bacteria from harsh conditions, including antibiotics and disinfectants. Detecting biofilms in an animal during an infection was a surprise.In research published today in Curli are a special type of protein called amyloids. Similar human proteins have been associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Scientists don't know how these diseases start, but have speculated that something must "trigger" the accumulation of amyloids."We are the first to show that a food-borne pathogen can make these types of proteins in the gut," said White, a leading expert on Salmonella biofilms and curli amyloids."There has been speculation that bacteria can stimulate amyloid plaque formation in Alzheimer's, Parkinson's and ALS and contribute to disease progression. The discovery of curli in the gut could represent an important link, pointing to a potentially infectious cause for these diseases."Collaborator Çagla Tükel and her team from Temple University determined that the presence of curli led to autoimmunity and arthritis -- two conditions that are known complications of Salmonella infections in humans."In mice, these reactions were triggered within six weeks of infection, demonstrating that curli can be a major driver of autoimmune responses," said Tükel.The next step in the research is to confirm that this also occurs in humans, and test if other food-borne pathogens related to Salmonella can cause similar autoimmune reactions."This important discovery suggests that food-borne pathogens could initiate or worsen autoimmunity and have the potential to contribute to amyloid disorders such as Alzheimer's and Parkinson's disease," said VIDO-InterVac Director Dr. Volker Gerdts.
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Microbes
| 2,020 |
July 9, 2020
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https://www.sciencedaily.com/releases/2020/07/200709135607.htm
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A new look at deep-sea microbes
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Microbial cells are found in abundance in marine sediments beneath the ocean and make up a significant amount of the total microbial biomass on the planet. Microbes found deeper in the ocean, such as in hydrocarbon seeps, are usually believed to have slow population turnover rates and low amounts of available energy, where the further down a microbe is found, the less energy it has available.
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A new study published out of a collaboration with the University of Delaware and ExxonMobil Research and Engineering shows that perhaps the microbial communities found deeper in the seafloor sediments in and around hydrocarbon seepage sites have more energy available and higher population turnover rates than previously thought.Using sediment samples collected by ExxonMobil researchers, UD professor Jennifer Biddle and her lab group -- including Rui Zhao, a postdoctoral researcher who is the first author on the paper; Kristin Yoshimura, who received her doctorate from UD; and Glenn Christman, a bioinformatician -- worked on a study in collaboration with Zara Summers, an ExxonMobil microbiologist. The study, recently published in Biddle and her lab members received the frozen sediments, collected during a research cruise, from ExxonMobil and then extracted the DNA and sequenced it at the Delaware Biotechnology Institute (DBI).The samples Biddle's lab group studied were ones collected from deeper in hydrocarbon seeps that usually get ignored."Most people only look at the top couple of centimeters of sediment at a seep, but this was actually looking 10-15 centimeters down," said Biddle associate professor in the School of Marine Science and Policy in UD's College of Earth, Ocean and Environment. "We then compared seepage areas to non-seepage areas, and the environment looked really different."Inside the seep, the microbes potentially lead a fast, less efficient life while outside the seep, the microbes lead a slower but more efficient life. This could be attributed to what energy sources are available to them in their environment."Understanding deep water seep microbial ecology is an important part of understanding hydrocarbon-centric communities," said Summers.Biddle said that microbes are always limited by something in the environment, such as how right now during the quarantine, we are limited by the amount of available toilet paper. "Outside of the seep, microbes are likely limited by carbon, whereas inside the seep, microbes are limited by nitrogen," said Biddle.While the microbes found inside the seep seem to be racing to make more nitrogen to keep up and grow with their fellow microbes, outside of the seep, the researchers found a balance of carbon and nitrogen, with nitrogen actually being used by the microbes as an energy source."Usually, we don't think of nitrogen as being used for energy. It's used to make molecules, but something that was striking for me was thinking about nitrogen as a significant energy source," said Biddle.This difference between the microbes found inside the seeps and those found outside the seeps could potentially mirror how microbes behave higher in the water column.Previous research of water column microbes shows that there are different types of microbes: those that are less efficient and lead a more competition-based lifestyle where they don't use every single molecule as well as they could and those that are really streamlined, don't waste anything and are super-efficient."It makes me wonder if the microbes that are living at these seeps are potentially wasteful and they're fast growing but they're less efficient and the organisms outside of the seeps are a very different organism where they're way more efficient and way more streamlined," said Biddle, whose team has put in a proposal to go back out to sea to investigate further. "We want to look at these dynamics to determine if it still holds true that there is fast, less efficient life inside the seep and then slower, way more efficient life outside of the seep."In addition, Biddle said this research showed that the deeper sediments in the seepages are most likely heavily impacted by the material coming up from the bottom, which means that the seep could be supporting a larger amount of biomass than previously thought."We often think about a seep supporting life like tube worms and the things that are at the expression of the sediment, but the fact that this could go for meters below them really changes the total biomass that the seep is supporting," said Biddle. "One of the big implications for the seepage sites with regards to the influence of these fluids coming up is that we don't know how deep it goes in terms of how much it changes the impact of subsurface life."Summers added that these are interesting insights "when considering oil reservoir connectivity to, and influence on, hydrocarbon seeps."
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Microbes
| 2,020 |
July 7, 2020
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https://www.sciencedaily.com/releases/2020/07/200707134206.htm
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Researchers create air filter that can kill the coronavirus
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Researchers from the University of Houston, in collaboration with others, have designed a "catch and kill" air filter that can trap the virus responsible for COVID-19, killing it instantly.
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Zhifeng Ren, director of the Texas Center for Superconductivity at UH, collaborated with Monzer Hourani, CEO of Medistar, a Houston-based medical real estate development firm, and other researchers to design the filter, which is described in a paper published in The researchers reported that virus tests at the Galveston National Laboratory found 99.8% of the novel SARS-CoV-2, the virus that causes COVID-19, was killed in a single pass through a filter made from commercially available nickel foam heated to 200 degrees Centigrade, or about 392 degrees Fahrenheit. It also killed 99.9% of the anthrax spores in testing at the national lab, which is run by the University of Texas Medical Branch."This filter could be useful in airports and in airplanes, in office buildings, schools and cruise ships to stop the spread of COVID-19," said Ren, MD Anderson Chair Professor of Physics at UH and co-corresponding author for the paper. "Its ability to help control the spread of the virus could be very useful for society." Medistar executives are is also proposing a desk-top model, capable of purifying the air in an office worker's immediate surroundings, he said.Ren said the Texas Center for Superconductivity at the University of Houston (TcSUH) was approached by Medistar on March 31, as the pandemic was spreading throughout the United States, for help in developing the concept of a virus-trapping air filter.Luo Yu of the UH Department of Physics and TcSUH along with Dr. Garrett K. Peel of Medistar and Dr. Faisal Cheema at the UH College of Medicine are co-first authors on the paper.The researchers knew the virus can remain in the air for about three hours, meaning a filter that could remove it quickly was a viable plan. With businesses reopening, controlling the spread in air conditioned spaces was urgent.And Medistar knew the virus can't survive temperatures above 70 degrees Centigrade, about 158 degrees Fahrenheit, so the researchers decided to use a heated filter. By making the filter temperature far hotter -- about 200 C -- they were able to kill the virus almost instantly.Ren suggested using nickel foam, saying it met several key requirements: It is porous, allowing the flow of air, and electrically conductive, which allowed it to be heated. It is also flexible.But nickel foam has low resistivity, making it difficult to raise the temperature high enough to quickly kill the virus. The researchers solved that problem by folding the foam, connecting multiple compartments with electrical wires to increase the resistance high enough to raise the temperature as high as 250 degrees C.By making the filter electrically heated, rather than heating it from an external source, the researchers said they minimized the amount of heat that escaped from the filter, allowing air conditioning to function with minimal strain.A prototype was built by a local workshop and first tested at Ren's lab for the relationship between voltage/current and temperature; it then went to the Galveston lab to be tested for its ability to kill the virus. Ren said it satisfies the requirements for conventional heating, ventilation and air conditioning (HVAC) systems."This novel biodefense indoor air protection technology offers the first-in-line prevention against environmentally mediated transmission of airborne SARS-CoV-2 and will be on the forefront of technologies available to combat the current pandemic and any future airborne biothreats in indoor environments," Cheema said.Hourani and Peel have called for a phased roll-out of the device, "beginning with high-priority venues, where essential workers are at elevated risk of exposure (particularly schools, hospitals and health care facilities, as well as public transit environs such as airplanes)."That will both improve safety for frontline workers in essential industries and allow nonessential workers to return to public work spaces, they said.
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Microbes
| 2,020 |
July 7, 2020
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https://www.sciencedaily.com/releases/2020/07/200707113304.htm
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Flu in early life determines our susceptibility to future infections
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Early infections of influenza A can help predict how the virus will affect people across different ages in the future and could impact the effectiveness of flu vaccines, says a new study published today in
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The findings may help improve estimates of both the age-specific risk of acquiring seasonal influenza infections and vaccine effectiveness in similarly vaccinated populations.Seasonal influenza is an acute respiratory infection caused by influenza viruses that occur across the world. It causes approximately 100,000-600,000 hospitalisations and 5,000-27,000 deaths per year in the US alone. There are three types of seasonal influenza viruses in humans: A, B and C, although C is much less common. Influenza A viruses are further classified into subtypes, with the A(H1N1) and A(H3N2) subtypes currently circulating in humans. A(H1N1) is also written as A(H1N1)pdm09 as it caused the 2009 pandemic and replaced the A(H1N1) virus which had circulated before that year.The rapid evolution of seasonal influenza that allows it to escape preexisting immunity adds to the relatively high incidence of infections, including in previously infected older children and adults. But how susceptibility arises and changes over time in human populations has been difficult to quantify."Since the risk of influenza infection in a given age group changes over time, factors other than age may affect our susceptibility to infection," says first author Philip Arevalo, a postdoctoral researcher in senior author Sarah Cobey's lab, Department of Ecology and Evolution, University of Chicago, US. "We wanted to see whether these differences can be explained in part by the protection gained from childhood flu infection, which has lasting impacts on the immune response to future infections and the protection against new influenza A subtypes."To measure the effect of early exposures to seasonal influenza on risk and vaccine effectiveness, Arevalo and his team applied statistical models to flu cases identified through seasonal studies of vaccine effectiveness from the 2007-2008 to 2017-2018 seasons in the Marshfield Epidemiologic Study Area (MESA) in Marshfield, Wisconsin, US. Each flu season, individuals in a defined community group were recruited and tested for flu when seeking outpatient care for acute respiratory infection. Those eligible for the study were individuals older than six months of age living in MESA and who received routine care from the Marshfield Clinic.Despite the extensive evolution in influenza A subtypes H1N1 and H3N2 over the study period, the team's model showed that early infection reduces the risk of people needing to seek medical attention for infections with the same subtype later in life. This effect is stronger for H1N1 compared to H3N2. The model also revealed that the effectiveness of flu vaccines varies with both age and birth year, suggesting that this effectiveness also depends on early exposure."We hope the findings from our study will improve our understanding of influenza epidemiology and the low and variable effectiveness of the seasonal flu vaccine," concludes senior author Sarah Cobey, Principal Investigator at the Department of Ecology and Evolution, University of Chicago. "This would lead to better forecasting and vaccination strategies to help combat future flu seasons."
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Microbes
| 2,020 |
July 7, 2020
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https://www.sciencedaily.com/releases/2020/07/200707084000.htm
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Repurposing public health systems to decode COVID-19
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Existing public health monitoring systems in the UK could improve understanding of the risk factors associated with severe COVID-19.
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Research published in the journal The UK Biobank (UKB) is an international health resource which enables researchers to understand the genetic and lifestyle determinants of common diseases. The researchers linked UKB with Public Health England's Second-Generation Surveillance System (SGSS), a centralised microbiology database used for national disease surveillance in England. SGSS holds data collected in clinical diagnostic laboratories in England, including test results for SARS-CoV-2.Large cohorts such as UKB are a useful resource for understanding how a disease behaves in different groups, according to Dr Danny Wilson, Associate Professor at the Big Data Institute, University of Oxford (UK). He said: "Large datasets are helpful for detecting risk factors, including those that have modest effects or vary from person-to-person, and for providing a sound footing for conclusions by reducing statistical noise. These discoveries help scientists better understand the disease and could inspire efforts aimed at improving treatment."By linking the two systems, researchers hope to facilitate research into the risk factors for severe COVID-19. Repurposing public health systems in this way can provide near-to-real-time data on SARS-CoV-2, and allow researchers to understand the spread, testing and disease characteristics of the virus.This new computerised system will provide weekly linkage of test results to UKB and other cohorts. The UK Biobank database consists of around 500,000 men and women in the UK, aged 50+. This group is particularly appropriate for the study of COVID-19, as severity of disease increases with age. Further data is also being released by UKB, according to Dr Wilson: "UK Biobank are releasing, or have released other data relevant to COVID-19, like mortality records, and they plan to release hospital episode statistics and primary care data soon too."Their data provides in-depth analysis of disease severity, symptoms and risk in people from the UKB database. Researchers hope that this data can reveal additional risk factors for severe infection and improve understanding of the disease. "By providing information about COVID-19 to large cohorts including UK Biobank, INTERVAL, COMPARE, Genes & Health, Genomics England and the National Institute for Health Research (NIHR) Biorepository, this work facilitates research into lifestyle, medical and genetic risk factors" said Dr Wilson.
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Microbes
| 2,020 |
July 6, 2020
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https://www.sciencedaily.com/releases/2020/07/200706152703.htm
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Desert algae shed light on desiccation tolerance in green plants
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Deserts of the U.S. Southwest are extreme habitats for most plants, but, remarkably, microscopic green algae live there that are extraordinarily tolerant of dehydration. These tiny green algae (many just a few microns in size) live embedded in microbiotic soil crusts, which are characteristic of arid areas and are formed by communities of bacteria, lichens, microalgae, fungi, and even small mosses. After completely drying out, the algae can become active and start photosynthesizing again within seconds of receiving a drop of water.
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How are they so resilient? That question is at the core of research by Elena Lopez Peredo and Zoe Cardon of the Marine Biological Laboratory (MBL), published this week in Working with two particularly resilient species of green microalgae (Acutodesmus deserticola and Flechtneria rotunda), Peredo and Cardon studied up- and down-regulation of gene expression during desiccation, and added a twist. They also analyzed gene expression in a close aquatic relative (Enallax costatus) as it dried out and ultimately died. Surprisingly, all three algae -- desiccation tolerant or not -- upregulated the expression of groups of genes known to protect even seed plants during drought. But the desiccation-tolerant algae also ramped down expression of genes coding for many other basic cellular processes, seemingly putting the brakes on their metabolism. The aquatic relative did not.Peredo's and Cardon's research suggests this new perspective on desiccation tolerance warrants investigation in green plants more broadly. Upregulation of gene expression coding for protective proteins may be necessary but not sufficient; downregulation of diverse metabolic genes may also be key to survival.
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Microbes
| 2,020 |
July 6, 2020
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https://www.sciencedaily.com/releases/2020/07/200706094128.htm
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Harmful microbes found on sewer pipe walls
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Can antibiotic-resistant bacteria escape from sewers into waterways and cause a disease outbreak?
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A new Rutgers study, published in the journal They found that these biofilms often contain harmful, antibiotic-resistant bacteria and can withstand standard treatment to disinfect sewers. Cleaning with bleach can reduce the density of biofilms but not entirely remove them, potentially leaving wastewater treatment workers and the public exposed to health risks.Still, disinfecting a sewer line may be a good idea before sewer maintenance is done, especially following events such as a disease outbreak or bioterrorism incident that might expose sewer lines to high-risk microbes. Luckily, with respect to SARS-CoV-2, the coronavirus causing COVID-19, water and wastewater are not expected to be important transmission routes.Normally, what's flushed down a toilet goes to a wastewater treatment plant. But rainfall can cause overflows of untreated waste into bays, rivers, streams and other waterways. The researchers say a potential worst-case scenario would be an infectious disease outbreak following a sewer overflow that releases wastewater, sewer solids and biofilms to surface water."Given the current interest in wastewater-based epidemiology for monitoring the coronavirus, our study highlights the need to consider sewer processes and how best to combat pathogens," said senior author Nicole Fahrenfeld, an associate professor in the Department of Civil and Environmental Engineering in the School of Engineering at Rutgers University-New Brunswick. "We will work to repeat a portion of our experiments to understand how long the coronavirus may linger in sewers and if that will impact monitoring of it in wastewater."The researchers found that sewer pipe materials (concrete or PVC plastic) did not affect the formation of biofilms but played a role in the effectiveness of bleach to disinfect them. Bleach is better at removing biofilms from PVC than from concrete, likely because PVC is smoother.The lead author is William R. Morales Medina, a Rutgers doctoral student. Alessia Eramo, who earned a doctorate at Rutgers, and Melissa Tu, a Rutgers undergraduate student, contributed to the study.
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Microbes
| 2,020 |
July 2, 2020
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https://www.sciencedaily.com/releases/2020/07/200702144715.htm
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Scientists reveal why tummy bugs are so good at swimming through your gut
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Researchers have solved the mystery of why a species of bacteria that causes food poisoning can swim faster in stickier liquids, such as within guts.
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The findings could potentially help scientists halt the bacteria in its tracks, because they show how the shape of the bacteria's body and the components that help it swim are all dependent on each other to work. This means any disruption to one part could stop the bacteria getting through to the gut.Now, researchers from Imperial College London, Gakushuin University in Tokyo and the University of Texas Southwestern Medical Center have filmed Co-first author Dr Eli Cohen, from the Department of Life Sciences at Imperial, said: "It seemed very strange that the bacteria had a tail at both ends -- it's like having two opposing motors at either end of a ship. It was only when we watched the bacteria in action that we could see how the two tails work cleverly together to help the bacteria move through the body."The team created To change direction, they changed which flagella were wrapped around their body, enabling quick 180 degree turns and potential escape from confined spaces.They also found that the process of wrapping the flagella was easier when swimming through viscous liquids; the stickiness helping push the leading flagella back around the body. In less-viscous liquids neither flagella were able to wrap around the body.Lead researcher Dr Morgan Beeby, from the Department of Life Sciences at Imperial, said: "Our study kills two birds with one stone: in setting out to understand how "As well as solving some long-standing mysteries, the research could also help researchers find new way to prevent infection by The research also revealed that the helical shape of the bacteria body is crucial for allowing the flagella to wrap around it, showing how the two components are reliant on each other. This adds to the team's previous work showing how parts of the 'motor' that drives the flagella are co-dependent, and that none would work without the others.
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Microbes
| 2,020 |
July 2, 2020
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https://www.sciencedaily.com/releases/2020/07/200702113700.htm
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Algae as living biocatalysts for a green industry
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Better still: living algae can be used as biocatalysts for certain substances, and they bring the co-substrate along, producing it in an environmentally friendly manner through photosynthesis. The team published its report in
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Many chemical substances in cosmetics, food or medicines can assume slightly different three-dimensional structures, with only one of them generating the desired fragrance or medical effect. The chemical production of the right substances is often not environmentally friendly, as it requires high temperatures or special solvents. In nature, however, certain proteins do exist that produce the required product at mild temperatures and in water. In the process, they often generate exactly the 3D structure of the substance that is needed by the industry.These so-called old yellow enzymes, OYEs for short, owe their name to their naturally yellow colour. They occur in bacteria, fungi and plants, are in part well studied and offer considerable potential for a bio-based economy. However, they have one disadvantage: in order to carry out their reaction, they need the co-substrate NADPH (nicotinamide adenine dinucleotide phosphate). In living cells, this small molecule is generated through metabolic processes, whereas its chemical production is very expensive; as a result, the commercial use of OYEs is thwarted.The research team from Bochum has discovered several OYEs in unicellular green algae. "For a broad application, industry needs OYEs that can also produce unusual molecules," explains Professor Thomas Happe, Head of the Photobiotechnology research group at RUB. "Algae possess very complex metabolic pathways and are therefore ideal sources for novel biocatalysts." The researchers analysed algal OYEs in the test tube and showed that they are able to convert many commercially viable substances. "The exciting thing is that living algae can also carry out the reactions needed in the industry," points out PhD student Stefanie Böhmer, lead author of the study. "Since algae produce NADPH using photosynthesis, i.e. with sunlight, the co-substrate of the OYEs is supplied in an environmentally friendly and cost-effective way."The authors point out that the study demonstrates the importance of the collaboration between researchers from different disciplines, and that the industry can be a valuable partner who initiates basic research. Four researches from the Research Training Group "Micon -- Microbial substrate conversion," which is funded by the German Research Foundation, contributed their expertise to the study. The project was the brainchild of Solarbioproducts Ruhr, a spin-off established by Wirtschaftsförderungsgesellschaft Herne and Thomas Happe with the aim of developing concepts for environmentally friendly algae biotechnologies. "We have taken a big step towards a green industry," concludes Happe. "This would not have been possible without collaboration."
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Microbes
| 2,020 |
June 29, 2020
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https://www.sciencedaily.com/releases/2020/06/200629140054.htm
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Raw milk may do more harm than good
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Raw or unpasteurized cows' milk from U.S. retail stores can hold a huge amount of antimicrobial-resistant genes if left at room temperature, according to a new study from researchers at the University of California, Davis. The study also found bacteria that harbored antimicrobial-resistant genes can transfer them to other bacteria, potentially spreading resistance if consumed. The study was published in the journal Microbiome.
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"We don't want to scare people, we want to educate them. If you want to keep drinking raw milk, keep it in your refrigerator to minimize the risk of it developing bacteria with antibiotic-resistant genes," said lead author Jinxin Liu, a postdoctoral researcher in the Department of Food Science and Technology at UC Davis.An estimated 3 percent of the U.S. population consumes unpasteurized, or raw, milk, which has not been heated to kill pathogens and extend shelf life. Raw milk is often touted to consumers as having an abundant supply of probiotics, or healthy bacteria, compared with pasteurized milk. UC Davis researchers did not find that to be the case."Two things surprised us," said Liu. "We didn't find large quantities of beneficial bacteria in the raw milk samples, and if you leave raw milk at room temperature, it creates dramatically more antimicrobial-resistant genes than pasteurized milk."Bacteria with antimicrobial-resistant genes, if passed to a pathogen, have the potential to become "superbugs," so that pharmaceuticals to treat infection or disease no longer work. Each year, almost 3 million people get an antibiotic-resistant infection, and more than 35,000 people die, according to the Centers for Disease Control.UC Davis researchers analyzed more than 2,000 retail milk samples from five states, including raw milk and milk pasteurized in different ways. The study found raw milk had the highest prevalence of antibiotic-resistant microbes when left at room temperature."Our study shows that with any temperature abuse in raw milk, whether intentional or not, it can grow these bacteria with antimicrobial resistance genes," said co-author Michele Jay-Russell, research microbiologist and manager with the UC Davis Western Center for Food Safety. "It's not just going to spoil. It's really high risk if not handled correctly."Some consumers are intentionally letting raw milk sit outside of the refrigerator at room temperature to ferment, in order to make what's known as clabber. Co-author and Peter J. Shields Chair of Dairy Food Science David Mills said if consumers eat raw milk clabber, they are likely adding a high number of antimicrobial-resistant genes to their gut."You could just be flooding your gastrointestinal tract with these genes," said Mills. "We don't live in an antibiotic-free world anymore. These genes are everywhere, and we need to do everything we can to stop that flow into our bodies."While more work is needed to fully understand whether antibiotic-resistant genes in raw milk translate into health risks for humans, Mills suggests that consumers instead use a starter culture if they want to ferment raw milk, which carries specific strains of bacteria to inoculate the milk.Other authors include Yuanting Zhu of UC Davis and Danielle Lemay of USDA ARS Western Human Nutrition Research Center. This study was funded with support from the National Institutes of Health and the Peter J. Shields Endowed Chair in Dairy Food Science.
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Microbes
| 2,020 |
June 29, 2020
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https://www.sciencedaily.com/releases/2020/06/200629132059.htm
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Microbiome confers resistance to cholera
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Cholera can kill within hours if left untreated, and it sickens as many as 4 million people a year. In a new article in the journal
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Bacteria live everywhere on the planet -- even inside the human body. UCR microbiologist Ansel Hsiao studies whether the bacteria living in our bodies, collectively known as the human microbiome, can protect people from diseases caused by external bacteria such as Hsiao's team examined the gut microbiomes from people in Bangladesh, where many suffer from cholera as a result of contaminated food, water and poor sanitation infrastructure. "When people get sick, the diarrhea gets flushed into water systems that people drink from, and it's a negative cycle," Hsiao explained.His team wanted to see whether prior infections or other stresses, like malnutrition, make people more vulnerable, as compared to Americans who don't face these same pressures.The findings surprised the group, which expected stressed Bangladeshi microbiomes would allow for higher rates of infection. Instead, they saw infection rates varied greatly among individuals in both populations, suggesting susceptibility is based on a person's unique microbiome composition -- not the place they're from."Because bile is specific to the intestines of humans and animals, many microorganisms, including Once Hsiao's team identified one bacterium in the human microbiome, Since it's become clear that more Similar studies are also underway with regard to the virus causing another global pandemic -- SARS-CoV-2. Hsiao is collaborating with several groups trying to understand how the microbiome changes with COVID-19 infection."One day, we may also understand whether and how the microbiome affects COVID-19 and makes people resistant to other illnesses we don't currently have treatments for," Hsiao said.
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Microbes
| 2,020 |
June 29, 2020
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https://www.sciencedaily.com/releases/2020/06/200629120129.htm
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Clostridium difficile: Fecal microbial transplantation more effective and less costly than antibiotics
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An innovative treatment for patients with
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CDI is an infection of the bowel, which commonly affects people who have recently been treated in hospital, those with underlying conditions and patients over 65. Almost 30 per cent of patients treated for the condition experience at least one recurrence. A recurrence of the condition, has been associated with a higher risk of mortality and is usually treated using antibiotics.Faecal microbial transplantation (FMT), a treatment pioneered as a licenced medicine by Professor Peter Hawkey and his team at the University of Birmingham, is a method where gut bacteria and other components in faeces are used to treat CDI. The bacteria is taken from a screened healthy donor, processed and screened before being transplanted via a tube passed through the nose into the stomach. Treatment with FMT is associated with higher cure and lower recurrence rates than fidaxomicin or vancomycin- the two most common antibiotics used to treat recurrent CDI (rCDI).The study, which presents the first decision model for patients with rCDI already hospitalised in the UK, analysed randomised controlled trials, observational studies and expert opinion from the UK, on patients with single or multiple rCDI. Researchers analysed the cost of each of the four treatment options for rCDI for treatment effects, unit costs, resource and health related quality of life to identify which treatment was the most cost-effective and offered the best outcome for patients.The study showed that both methods for administering FMT were lower in cost compared to standard treatment with antibiotics. FMT via naso-gastric tube was the least costly, with a mean cost of £8,877 per patient, while FMT via colonoscopy was £11,716 per patient. FMT via colonoscopy was also shown to be slightly more effective than treatment via naso-gastric tube, offering patients a higher quality of life. Two other standard antibiotic treatments vancomycin and fidaxomicin were compared in the model but both these treatments were shown to be more costly and less effective than either of the FMT interventions. Moreover, Vancomycin was the most expensive and the least effective treatment.Professor Peter Hawkey, formerly of the University of Birmingham said, "We at the University of Birmingham pioneered this treatment as the UK's first third party FMT service. FMT is not currently a widespread treatment for this disease but by showing that it not only saves lives, but is also significantly more cost effective, we hope that this could be one of the first steps towards the treatment being accepted more widely."Professor Tracy Roberts, Head of the University of Birmingham's Health Economics Unit said "As well as being more effective both in terms of cost and benefit to patients, FMT was shown to significantly reduce the amount of days patients were required to be hospitalised which could also provide longer term cost-savings"
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Microbes
| 2,020 |
June 26, 2020
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https://www.sciencedaily.com/releases/2020/06/200626125023.htm
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Designer peptides show potential for blocking viruses, encourage future study
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Chemically engineered peptides, designed and developed by a team of researchers at Rensselaer Polytechnic Institute, could prove valuable in the battle against some of the most persistent human health challenges.
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The team's findings, recently published in Nature This foundational research lays the groundwork for further study into the ability of these peptides to provide an effective vehicle for therapeutics in the treatment of diseases such as Alzheimer's, Parkinson's, and cancer. The team's findings suggest the peptides may also prove valuable in providing a barrier between cells and viruses, such as the one that causes COVID-19 -- a possibility the research team now hopes to study."Because these peptides bind to PSA, they also mask PSA, and could potentially be used to inhibit the binding of viruses and their entry into cells," said Pankaj Karande, an associate professor of chemical engineering, a member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), and one of the lead authors on this paper. "The idea is to see if these peptides could inhibit that interaction and therefore inhibit the infectivity of those viruses."Taking inspiration from nature, Karande said the team modeled its peptides after proteins known as Sialic acid-binding immunoglobulin-type lectins, or Siglecs, which occur naturally and inherently bind to PSA.The research laid out in the paper was also led by Divya Shastry, a former doctoral student in biological sciences at Rensselaer. It was completed in collaboration with Robert Linhardt, an endowed professor of chemistry and chemical biology, and Mattheos Koffas, an endowed professor of chemical and biological engineering, both of whom are members of CBIS as well. The Rensselaer team also worked with a team from Syracuse University that used computational modeling to provide the Rensselaer researchers with a molecular-level look at the peptides they designed."These significant and promising research advances are a prime example of how a collaborative approach can solve persistent human health challenges," said Deepak Vashishth, the director of CBIS.
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Microbes
| 2,020 |
June 25, 2020
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https://www.sciencedaily.com/releases/2020/06/200625162248.htm
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Microbiome of anticancer compound-producing marine invertebrate
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Could the cure for melanoma -- the most dangerous type of skin cancer -- be a compound derived from a marine invertebrate that lives at the bottom of the ocean? A group of scientists led by Alison Murray, Ph.D. of the Desert Research Institute (DRI) in Reno think so, and are looking to the microbiome of an Antarctic ascidian called Synoicum adareanum to better understand the possibilities for development of a melanoma-specific drug.
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Ascidians, or "sea squirts," are primitive, sac-like marine animals that live attached to ocean-bottoms around the world, and feed on plankton by filtering seawater. S. adareanum, which grows in small colonies in the waters surrounding Antarctica, is known to contain a bioactive compound called "Palmerolide A" with promising anti-melanoma properties -- and researchers believe that the compound is produced by bacteria that are naturally associated with S. adareanum.In a new paper published this month in the journal Marine Drugs, Murray and collaborators from the University of South Florida, the Los Alamos National Laboratory, and the Université de Nantes, France, present important new findings measuring palmerolide levels across samples collected from Antarctica's Anvers Island Archipelago and characterizing the community of bacteria that make up the microbiome of S. adareanum."Our longer-term goal is to figure out which of the many bacteria within this species is producing palmerolide, but to do this, there is a lot we need to learn about the microbiome of S. adareanum," Murray said. "Our new study describes many advances that we have made toward that goal over the last few years."In 2008, Murray worked with Bill Baker, Ph.D., of the University of South Florida, and DRI postdoctoral researcher Christian Riesenfeld, Ph.D., to publish a study on the microbial diversity of one individual S. adareanum. Their new study builds upon this research by characterizing the microbial diversity of 63 different individuals that were collected from around Anvers Island.Their results identify a what the researchers call the "core microbiome" of the species -- a common suite of 21 bacterial taxa that were present in more than 80 percent of samples, and six bacterial taxa that were present in all 63 samples."It is a key "first" for Antarctic science to have been able to find and identify this core microbiome in a fairly large regional study of these organisms," Murray said. "This is information that we need to get to the next step of identifying the producer of palmerolide."Another "first" for Antarctic science, and for the study of natural products in nature in general, was a comparison of palmerolide levels across all 63 samples that showed the compound was present in every specimen at high (milligram per gram specimen tissue) levels, but the researchers found no trends between sites, samples, or microbiome bacteria. Additional analysis looking at the co-occurrence relationships of the taxa across the large data set showed some of the ways that bacteria are interacting with each other and with the host species in this marine ecosystem."The microbiome itself is unique in composition from other ascidians, and seems to be pretty interesting, with a lot of interaction," Murray said. "Our study has opened the doors to understand the ecology of this system."From the assemblage of bacteria that the researchers have identified as making up the core microbiome of S. adareanum, they next hope to use a genomics approach to finally be able to identify which of the bacteria are producing palmerolide -- an important and needed advancement toward the development of a melanoma treatment."It would be a really big deal to use this compound to develop a drug for fighting melanoma, because there are just so few drugs at the moment that can be used to treat it," Murray said. "If we can identify the bacteria that produce this chemical, and with its genome understand how to cultivate it in a laboratory setting, this would enable us to provide a sustainable supply of palmerolide that would not rely on harvesting wild populations of this species in Antarctica."
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Microbes
| 2,020 |
June 25, 2020
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https://www.sciencedaily.com/releases/2020/06/200625122735.htm
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Driving bacteria to produce potential antibiotic, antiparasitic compounds
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Researchers have developed a method to spur the production of new antibiotic or antiparasitic compounds hiding in the genomes of actinobacteria, which are the source of drugs such as actinomycin and streptomycin and are known to harbor other untapped chemical riches. The scientists report their findings in the journal
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The researchers wanted to overcome a decades-old problem that confronts those hoping to study and make use of the countless antibiotic, antifungal and antiparasitic compounds that bacteria can produce, said Satish Nair, a University of Illinois at Urbana-Champaign professor of biochemistry who led the research."In laboratory conditions, bacteria don't make the number of molecules they have the capability of making," he said. "And that's because many are regulated by small-molecule hormones that aren't produced unless the bacteria are under threat."Nair and his colleagues wanted to determine how such hormones influence the production of antibiotics in actinobacteria. By exposing their bacteria to the right hormone or combination of hormones, the researchers hope to spur the microbes to produce new compounds that are medically useful.The team focused on avenolide, a hormone that is more chemically stable than one used in earlier studies of bacterial hormones. Avenolide regulates the production of an antiparasitic compound known as avermectin in a soil microbe. A chemically modified version of this compound, ivermectin, is used as a treatment for river blindness, a disease transmitted by flies that blinded millions of people, mostly in sub-Saharan Africa, before the drug was developed.For the new study, chemistry graduate student Iti Kapoor developed a more streamlined process for synthesizing avenolide in the lab than was previously available. This allowed the team to study the hormone's interactions with its receptor both inside and outside bacterial cells."Using a method called X-ray crystallography, Iti and biochemistry graduate student Philip Olivares were able to determine how the hormone binds to its receptor and how the receptor binds to the DNA in the absence of hormones," Nair said. "Typically, these receptors sit on the genome and they basically act as brakes."The researchers discovered that when the hormone binds to it, the receptor loses its ability to cling to DNA. This turns off the brakes, allowing the organism to churn out defensive compounds like antibiotics.Knowing which regions of the receptor are involved in binding to the hormone and to the DNA enabled the team to scan the genomes of dozens of actinobacteria to find sequences that had the right traits to bind to their receptor or to similar receptors. This process, called genome mining, allowed the team to identify 90 actinobacteria that appear to be regulated by avenolide or other hormones in the same class."Our long-term project is to take those 90 bacteria, grow them up in the laboratory, add chemically synthesized hormones to them and see what new molecules are being produced," Nair said. "The beauty of our approach is that we can now get the bacteria to produce large quantities of molecules that normally we would not be able to make in the lab."Some of these new compounds are likely to have medical relevance, he said.
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Microbes
| 2,020 |
June 25, 2020
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https://www.sciencedaily.com/releases/2020/06/200625102524.htm
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Superbug impact on the gut
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Monash University researchers have discovered that the devastating bacterial superbug
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The infection is very difficult to treat, and often repeatedly reoccurs in patients even after they have been given powerful and debilitating antibiotics for many months. C. difficile is also highly resistant to antibiotics, which greatly complicates treatment.A team based in the Monash Biomedicine Discovery Institute (BDI) found that C. difficile massively activates a human enzyme called plasminogen in order to destroy gut tissue and to help spread the infection throughout the patient. Ordinarily, plasminogen, and its active form plasmin, is deployed in a highly controlled fashion to break down scar tissue and help wounds heal."The results were a huge surprise, and revealed that the severe damage caused to the gut by C. difficile was actually caused by a human enzyme rather than a bacterial toxin," said study co-leader and infectious disease expert Prof Dena Lyras.Given their findings, the researchers decided to investigate whether potent antibodies developed by the team and that inhibited the plasminogen / plasmin system could be used to treat the disease."We found that an antibody that prevented plasminogen from being activated dramatically stalled the progress of infection and tissue damage," said first author Milena Awad.The researchers now aim to commercialise their antibodies in order to treat a range of bacterial and inflammatory diseases.An advantage of targeting a human protein in an infectious disease is that resistance to the therapy is far less likely to occur."The antibody could have broad utility, since the plasminogen / plasmin system is dysregulated in a range of different serious inflammatory and infectious diseases -- for example, the plasminogen system most likely is a driver of the devastating lung damage seen in COVID-19," said study co-leader and structural biologist Prof James Whisstock.
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Microbes
| 2,020 |
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