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December 14, 2020 | https://www.sciencedaily.com/releases/2020/12/201214192400.htm | Type and abundance of mouth bacteria linked to lung cancer risk in non-smokers | The type and abundance of bacteria found in the mouth may be linked to lung cancer risk in non-smokers, finds the first study of its kind, published online in the journal | Fewer species and high numbers of particular types of bacteria seem to be linked to heightened risk, the findings indicate.Around one in four cases of lung cancer occurs in non-smokers and known risk factors, such as second hand tobacco smoke, background radon exposure, air pollution, and family history of lung cancer don't fully explain these figures, say the researchers.The type and volume of bacteria (microbiome), found in the mouth has been associated with a heightened risk of various cancers including those of the gullet, head and neck, and pancreas.And the researchers wanted to find out if this association might also hold for lung cancer, given that the mouth is the entry point for bacteria to the lungs.They drew on participants in The Shanghai Women's Health Study and the Shanghai Men's Health Study, all of whom were lifelong non-smokers, and whose health was monitored every 2-3 years after entry to the study between 1996 and 2006.At enrolment, participants rinsed out their mouths to provide a profile of the resident bacteria, and information was obtained on lifestyle, diet, medical history and other environmental and workplace factors that might influence their disease risk.In all, 90 of the women and 24 of the men developed lung cancer within around 7 years, on average.These cases were matched with 114 non-smokers of the same age and sex, who also provided a mouth rinse sample. This comparison group didn't have lung cancer but they had similar levels of education and family histories of lung cancer.Comparison of both sets of rinse samples showed that the microbiome differed between the two groups. A wider range of bacterial species was associated with a lower risk of developing lung cancer. And a larger volume of particular types of species was also associated with lung cancer risk.A larger volume of Bacteroidetes and Spirochaetes species was associated with lower risk while a larger volume of Firmicutes species was associated with heightened risk.Specifically, within the Spirochaetes species, a greater abundance of Spirochaetia was associated with lower risk; and within the Firmicutes species, a larger volume of organisms from the The associations remained when the analysis was restricted to those participants who had not taken any antibiotics in the 7 days before sample collection and after excluding those diagnosed with lung cancer within 2 years of sample provision.This is an observational study, and therefore can't establish cause. And the researchers acknowledge several limitations. "While our study provides evidence that variation in the oral microbiome plays a role in lung cancer risk, the interpretation of our study must be done while considering the caveat that our findings are from a single time point in a single geographical location," they write.In a linked editorial, Dr David Christiani, of Harvard University, suggests that mouth bacteria may provoke chronic inflammation, boost cell proliferation and inhibit cell death, prompt DNA changes, and switch on cancer genes and their blood supply, which would help to explain the findings.The study findings raise several questions, he says. "First, how stable is the human oral microbiome over time? Second, if the human oral microbiome varies over time, what determines that variability? Third, how does the ambient environment such as exposure to air pollutants, affect the oral (and lung) microbiome?"He adds: "It remains unclear whether the oral microbiome as measured in this (and other) epidemiological studies represents a causative agent or only a marker of disease or immune activity. If it is the former, then it will be important to understand whether the oral microbiome actually seeds the lung microbiome and thus acts locally." | Microbes | 2,020 |
December 14, 2020 | https://www.sciencedaily.com/releases/2020/12/201214164328.htm | UV-emitting LED lights found to kill coronavirus | Researchers from Tel Aviv University (TAU) have proven that the coronavirus can be killed efficiently, quickly, and cheaply using ultraviolet (UV) light-emitting diodes (UV-LEDs). They believe that the UV-LED technology will soon be available for private and commercial use. | This is the first study conducted on the disinfection efficiency of UV-LED irradiation at different wavelengths or frequencies on a virus from the family of coronaviruses. The study was led by Professor Hadas Mamane, Head of the Environmental Engineering Program at TAU's School of Mechnical Engineering, Iby and Aladar Fleischman Faculty of Engineering. The article was published in November 2020 issue of the "The entire world is currently looking for effective solutions to disinfect the coronavirus," said Professor Mamane. "The problem is that in order to disinfect a bus, train, sports hall, or plane by chemical spraying, you need physical manpower, and in order for the spraying to be effective, you have to give the chemical time to act on the surface. Disinfection systems based on LED bulbs, however, can be installed in the ventilation system and air conditioner, for example, and sterilize the air sucked in and then emitted into the room."We discovered that it is quite simple to kill the coronavirus using LED bulbs that radiate ultraviolet light," she explained. "We killed the viruses using cheaper and more readily available LED bulbs, which consume little energy and do not contain mercury like regular bulbs. Our research has commercial and societal implications, given the possibility of using such LED bulbs in all areas of our lives, safely and quickly."The researchers tested the optimal wavelength for killing the coronavirus and found that a length of 285 nanometers (nm) was almost as efficient in disinfecting the virus as a wavelength of 265 nm, requiring less than half a minute to destroy more than 99.9% of the coronaviruses. This result is significant because the cost of 285 nm LED bulbs is much lower than that of 265 nm bulbs, and the former are also more readily available.Eventually, as the science develops, the industry will be able to make the necessary adjustments and install the bulbs in robotic systems or air conditioning, vacuum, and water systems, and thereby be able to efficiently disinfect large surfaces and spaces. Professor Mamane believes that the technology will be available for use in the near future.It is important to note that it is very dangerous to try to use this method to disinfect surfaces inside homes. To be fully effective, a system must be designed so that a person is not directly exposed to the light.In the future, the researchers will test their unique combination of integrated damage mechanisms and more ideas they recently developed on combined efficient direct and indirect damage to bacteria and viruses on different surfaces, air, and water.The study was conducted in collaboration with Professor Yoram Gerchman of Oranim College; Dr. Michal Mandelboim, Director of the National Center for Influenza and Respiratory Viruses at Sheba Medical Center at Tel HaShomer; and Nehemya Friedman from Tel Hashomer. | Microbes | 2,020 |
December 10, 2020 | https://www.sciencedaily.com/releases/2020/12/201210145847.htm | Persistence of Zika virus in the brain causes long-term problems in mice | The Zika virus can remain in mouse brain for extended periods, leading to long-term neurological and behavioral consequences, according to a study published December 10 in the open-access journal | Infections in the perinatal period are associated with lasting cognitive impairment and increased risk for psychological disorders. The congenital brain malformations associated with Zika virus infections early in pregnancy are well documented. But the potential defects and long-term consequences associated with milder infections in late pregnancy and the perinatal period are less well understood. To address this knowledge gap, Verthelyi and colleagues exposed one-day-old mice to the Zika virus and monitored the neurological and behavioral consequences up to one year later.The animals developed a transient neurological syndrome characterized by unsteady gait, tremors, and seizures 10 to 15 days after infection, but these symptoms subsided after one week, and most animals survived. Despite apparent recovery, Zika virus and inflammation were detected in the central nervous system of mice one year later. These older mice showed reduced volume of a brain region called the cerebellum, resulting in significant long-term deficits in motor function and coordination. In addition, the older mice showed anxiety, hyperactivity, and impulsive or risky behavior. Based on these findings, the authors recommend long-term neurological and behavioral monitoring of patients exposed to the virus at an early age, as well as anti-viral treatment to clear persistent reservoirs from the brain.The authors conclude, "There is mounting evidence that emerging viruses like Zika and Chikungunya can establish reservoirs in immune privileged sites and play a role in development of chronic diseases." | Microbes | 2,020 |
December 9, 2020 | https://www.sciencedaily.com/releases/2020/12/201209191433.htm | Toxin provides clues to long-term effects of diarrhea caused by E. coli | For people in wealthy countries, diarrhea is usually nothing more than an uncomfortable inconvenience for a few days. But for a poor child in a developing country, repeated bouts of diarrhea can lead to serious health consequences such as malnutrition, stunted growth and cognitive deficits. | Researchers at Washington University School of Medicine in St. Louis have discovered that a toxin produced by the bacterium Escherichia coli (E. coli), long known to cause diarrhea, also has other effects on the human digestive tract. The toxin, they found, changes gene expression in the cells that line the inside of the gut, inducing them to manufacture a protein that the bacterium then uses to attach to the intestinal wall.The findings, published Nov. 17 in "There's more than meets the eye with this toxin," said senior author James M. Fleckenstein, MD, a professor of medicine and of molecular microbiology. "It is basically changing the surface of the intestine to benefit itself, probably ultimately to the detriment of the host. Decades ago, people worked out how the toxin causes diarrhea, but until recently, nobody really had the tools to delve into what else this toxin might be doing. We're trying to put together the pieces of the puzzle to find out how toxin-producing E. coli might be driving malnutrition and other ripple effects of diarrhea."Fleckenstein and first author Alaullah Sheikh, PhD, a postdoctoral researcher, study enterotoxigenic E. coli (ETEC), a toxin-producing strain of E. coli that is a common cause of severe, watery diarrhea. The bacterium's so-called heat-labile toxin causes ion channels on intestinal cells to open, triggering an outpouring of water and electrolytes into the digestive tract -- in other words, diarrhea.Since oral rehydration therapy was invented in the 1970s, deaths from diarrhea have dropped by more than 80% worldwide. While invaluable at helping people survive a bout of diarrhea, the therapy does nothing to reduce the number of cases. Worldwide, young children still develop diarrhea an average of three times a year, with the youngest and poorest children bearing the brunt of the caseload -- and of the long-term health consequences.Fleckenstein and Sheikh speculated that ETEC's heat-labile toxin might be doing more than just causing acute diarrhea and dehydration. If so, it might explain the link between ETEC and malnutrition, stunting and other problems.To find other ways the toxin affects the gut, the researchers grew human intestinal cells in a dish and treated the cells with the toxin. They found that the toxin activates a set of genes known as CEACAMs. One in particular -- CEACAM6 -- codes for a protein that is normally in cells of the small intestine at low levels. Further experiments revealed that the toxin causes cells to produce more CEACAM6 protein, which the bacteria then uses to attach to intestinal cells and deliver even more toxin. Moreover, using intestinal biopsy specimens from people in Bangladesh infected with ETEC, the researchers showed that CEACAM6 expression increases in the small intestine during natural infection."CEACAM6 is expressed in what is called the brush border of the small intestine, which is where all your vitamins and nutrients get absorbed," Sheikh said. "This is one of the first pieces of evidence that ETEC can change the intestinal surface. We don't yet know how long that lasts and what that means for people who are infected, but it stands to reason that damage to this part of the body could affect the ability to absorb nutrients."Fleckenstein, Sheikh and colleagues are continuing to study the link between ETEC and malnutrition, stunting and other health consequences."We are trying in the lab to understand the role of ETEC and its toxins as they relate to nondiarrheal effects of ETEC infection, particularly in young children in developing countries," Fleckenstein said. "There's a lot of work to be done to explore how the toxins might be related to these long-term consequences of diarrhea." | Microbes | 2,020 |
December 9, 2020 | https://www.sciencedaily.com/releases/2020/12/201209191359.htm | Insecure livelihoods hindering efforts to combat anti-microbial resistance globally | Patients living in precarious circumstances are less likely to use antibiotics appropriately according to a new study from the University of Warwick, suggesting that efforts to improve conditions for those with little security in their livelihoods could have an unexpected benefit in helping to tackle antimicrobial resistance globally. | The findings add to evidence that focus should shift from influencing individuals' efforts to combat anti-microbial resistance to supporting sustainable development policy that tackles the contributing factors.The research, published in the journal Precarity refers to personal circumstances dominated by uncertainty, whether that is in employment, your personal life or social status. Those in precarious circumstances are limited in their ability to plan ahead, and deprived of safety nets, social support, economic certainty and flexibility. It is not necessarily about being poor: although this study looked at low to middle income countries, precarity can also be a problem in higher income countries.Using statistical analysis, the researchers were able examine the impact of socioeconomic factors, such as precarity, poverty and marginalisation, on their use of antibiotics to treat their illness. They found that patients in precarious circumstances had a chance of up to 51% of using antibiotics without advice from a medical professional or for inappropriate illnesses -- compared to 17% for an average patient.Lead author Dr Marco Haenssgen, from the Warwick Institute of Advanced Study and the Department of Global Sustainable Development, argues that this behaviour is understandable as when living in precarious circumstances individuals are engaged in a constant balancing act.Dr Haenssgen, Assistant Professor in Global Sustainable Development, said: "You have to balance your health, your economic life, feed your family, go to school; these are all competing priorities."Antibiotics have become such a staple of healthcare that they have become what some people see as a 'quick fix' solution. When people are in precarious circumstances and deprived of social support, if they can find a quick fix to keep them going they will use it, and then it could become problematic."In many low to middle income countries, patients often have to travel long distances to access healthcare services, something they may not be able to easily arrange or afford. Even in more economically developed areas, employment can be less secure and social networks can be eroded.Antimicrobial resistance occurs when microbes become resistant to antibiotics, threatening their effectiveness. Human antibiotic use is known to be a main driver of this process, and policies to combat anti-microbial resistance have therefore typically focused on clinical factors and promoting individual responsibilities. However, the researchers argue that the impact of socioeconomic factors such as precarity are being underestimated.Dr Haenssgen said: "You cannot always blame the individual for misuse of antibiotics. Often, we find ourselves in living conditions that provoke problematic behaviours, which means that if you want to improve antibiotic use you need to improve those living conditions."If we can improve situations of precarity then we have a good start for future interventions. We have a very substantial facet of the problem that is continuously disregarded and where potentially we have a lot of gains to realise."Antimicrobial resistance is a massive global health problem, it can potentially overturn what global health is. Many of the past gains that we have had in infectious disease control and prevention are potentially being undone by antimicrobial resistance."The study focused on five local communities across rural Thailand and Lao People's Democratic Republic and surveyed 2066 residents on recent illnesses they had experienced and how they sought healthcare support for it. This provided the researchers with a rich dataset on 1421 illness episodes that they could analyse to determine what healthcare patients seek, if any, whether they were able to access suitable healthcare, and when these occur in the timeline of their illness. | Microbes | 2,020 |
December 9, 2020 | https://www.sciencedaily.com/releases/2020/12/201209170633.htm | Hydrogen peroxide keeps gut bacteria away from the colon lining | Scientists at UC Davis Health have discovered that an enzyme in the colon lining releases hydrogen peroxide (H | Most microbes reside in the large intestine, a naturally low-oxygen environment. They form a community called the gut microbiota."More than half of the human body consists of microbes that do not tolerate oxygen very well," said Andreas Bäumler, professor of medical microbiology and immunology and lead author on the study.The gut microbiota is kept away from the colon's surface. This separation is essential to avoid inflammation caused by unnecessary immune responses to gut microbes. Scientists believed the spatial separation is maintained by oxygen released by cells to prevent microbes from coming too close to the intestinal lining. This study upends that theory."We looked at the spatial relationships between the bacteria in the gut and its host, the colon," Bäumler said. "We found that cells in the colon's lining release hydrogen peroxide- not oxygen- to limit microbial growth."NOX1, an enzyme found in the intestinal lining, provides a significant source of HWhen the body experiences an imbalance in the gut microbial community, it suffers from dysbiosis, a gastrointestinal condition. Dysbiosis may cause inflammation and symptoms such as nausea, upset stomach and bloating. Traditional treatments of dysbiosis rely mainly on the use of antibiotics or probiotics to target the bacteria.Findings from the new study indicate the need for a different approach to treating gut inflammation and dysbiosis. They pointed to the opportunity of restoring host functions instead of eliminating microbes."We need to shift the focus of gut inflammation treatments from targeting bacteria to fixing habitat filters of the host and restoring their functionality," Bäumler said.Co-authors on this study are Brittany M. Miller, Megan J. Liou, Lillian F. Zhang, Henry Nguyen, Yael Litvak, Eva-Magdalena Schorr, Kyung Ku Jang, Connor R. Tiffany and Brian P. Butler.This work was supported by the Vaadia-BARD Postdoctoral Fellowship FI-505-2014, USDA/NIFA award 2015-67015-22930, Crohn's and Colitis Foundation of America Senior Investigator Award # 650976 and by Public Health Service Grants AI36309, AI044170, AI096528, AI112445, AI146432 and AI112949. | Microbes | 2,020 |
December 9, 2020 | https://www.sciencedaily.com/releases/2020/12/201209115207.htm | Battling COVID-19 using UV light | As the deadly COVID-19 pandemic continues to wreak havoc around the world with no end in sight, new ways in which to stop the spread or mitigate the effects of the disease are few. | Although most experts agree that a vaccine would significantly slow or eventually stop the spread, the work to develop, approve and distribute such a vaccine are likely months away. That leaves us with only prevention efforts such as masks, social distancing and disinfecting, which partially due to human inconsistencies in behavior, have proven to be variable in effectiveness.Despite these grim realities about the novel coronavirus that has taken 2020 by storm, disrupting the work, school and personal lives of nearly everyone on the globe, some University of New Mexico researchers have found a possible breakthrough in how to manage this virus, as well as future ones.A team led by the Center for Biomedical Engineering faculty David Whitten, Distinguished Professor in the Department of Chemical and Biological Engineering, along with Eva Chi and Linnea Ista, faculty members in the same department, have found some light at the end of the tunnel, so to speak.The main finding of their research, highlighted in the paper, "Highly Effective Inactivation of SARS-CoV-2 by Conjugated Polymers and Oligomers," published this week in the journal UNM co-authors on the paper were Florencia A. Monge, of UNM's Center for Biomedical Engineering and the biomedical engineering graduate program; Virginie Bondu of the Department of Molecular Genetics and Microbiology at the UNM School of Medicine; Alison M. Kell, Department of Molecular Genetics and Microbiology at the UNM School of Medicine; and Patrick L. Donabedian of the nanoscience and microsystems engineering graduate program at UNM. Also on the team are Kirk S. Schanze and Pradeepkumar Jagadesan, both of the Department of Chemistry at the University of Texas at San Antonio.Although disinfectants such as bleach or alcohol are effective against the virus, they are volatile and corrosive, which limit lasting sterilization of surfaces treated by these products, Whitten said.What is different about these polymer and oligomer materials is that when activated with UV light, they provide a coating that is shown to be fast acting and highly effective, reducing the concentration of the virus by five orders of magnitude, Chi said."These materials have shown to have broad-spectrum antiviral properties," she said.Whitten points out that in order for the material to be active against the virus, it must be exposed to light. Light activates the "docking" process that is important and necessary for placing the oligomer or polymer at the surface of the virus particle, allowing the absorption of light that generates the reactive oxygen intermediate at the surface of the virus particle."As far as we know so far, materials such as ours are not active against SARS-CoV-2 in the dark and require activation by irradiation with ultraviolet or visible light, depending on where the specific antimicrobial absorbs light," he said. "In the dark, our antimicrobial materials 'dock' with the virus, and then on irradiation, they activate oxygen. It is this active, excited state of oxygen that starts the chain of reactions that inactivate the virus."And this science can easily be applied into consumer, commercial and healthcare products, such as wipes, sprays, clothing, paint, personal protective equipment (PPE) for healthcare workers, and really almost any surface."When incorporated into N95 masks, this material works well against the virus," Chi said. "In addition to trapping the virus in a mask, this would make for better PPE and prolong its life."Another unique advantage of this material is that unlike traditional disinfectant products, it is shown to not wash away with water and leaves no toxic residue as a result of the photodegradation process, Chi said.Studying the potential of conjugated polymers and oligomers is nothing new for UNM researchers. In fact, Whitten and another of the authors on the study, Kirk Schanze, have been researching this area for a couple of decades.Whitten and Chi said colleagues such as Schanze and others have collected a lot of data on polymer and oligomers, so when the pandemic hit in the spring, Whitten almost immediately started wondering how his area of study could help."It was the right timing for all of us," Chi said.Acquiring live coronavirus for research is not an easy feat, but thanks to the efforts a couple of team members, they were able to make it happen.Linnea Ista is a member of the Biosafety Committee at UNM, and when the pandemic broke out and she was aware of the research that Whitten and Chi were conducting, she realized that she may have a connection on how to make the research happen, due to the fact that representatives from UNM's School of Medicine also sit on the committee.Alison Kell, a faculty member in the School of Medicine, was the one who was able to acquire the live coronavirus for testing the effectiveness of these materials. She has been working with the SARS-CoV-2 virus in her research and was able to develop a protocol for analyzing samples the team prepared and exposing them to near UV or visible light.Due to the sensitive nature of working with a virus such as coronavirus, it was crucial for Kell to be part of the team, since the work had to be done in cooperation with the UNM School of Medicine, which has BSL-3 lab facilities that are essential to doing study on the highly-contagious active virus, Ista said.Whitten said he is hopeful that this discovery can quickly be put into use. He has a company called BioSafe Defenses that he said has hired a former Environmental Protection Agency official to help expedite the regulatory process in taking this discovery to market. He anticipates that once a material is approved, it will be only a matter of months before wipes, masks and other products are in the marketplace.He said their research has found that adding the material into wipes would add only pennies per wipe. Additionally, the material could be added into masks and other personal protective equipment, changing the game for businesses such as gyms, airlines, cruise ships, groceries, health care facilities, schools and many more industries. In addition to coronavirus, these products could also help eliminate infections by the common cold, seasonal flu and other viral and bacterial infections that plague millions of people annually, causing loss of work and school time."There is a limitless market for this," he said.He added that the current pandemic is likely not the last such public health crisis we will see, so even after a vaccine for coronavirus is available, such products could be useful in combatting a wide variety of viruses and bacteria, including the flu or common cold."We're not just thinking about COVID but other pathogens and any viral agents," Whitten said. "We want to be ready for the next pandemic."This research was funded by a grant from the National Institutes of Health. | Microbes | 2,020 |
December 8, 2020 | https://www.sciencedaily.com/releases/2020/12/201208163000.htm | Vitamin boosts essential synthetic chemistry | Inspired by light-sensing bacteria that thrive near hot oceanic vents, synthetic chemists at Rice University have found a mild method to make valuable hydrocarbons known as olefins, or alkenes. | Like the bacteria, the researchers use vitamin B12, eliminating harsh chemicals typically needed to make precursor molecules essential to the manufacture of drugs and agrochemicals.The open-access work by Julian West, an assistant professor of chemistry, and his colleagues appears in the Royal Society of Chemistry journal "Arguably, these olefins, or alkenes, are the most useful functional groups in a molecule," said West, an assistant professor of chemistry recently named one of Forbes Magazine's 30 Under 30 rising stars in science. "A functional group is like a foothold in climbing: It lets you get to where you want to go, what you want to make."We've had methods to make olefins for a long time, but a lot of these classic methods -- late 19th or early 20th century -- use incredibly strong bases, things that would burn you and would definitely burn your molecule if it had anything sensitive on it," he said. "The other issue is that such harsh conditions might be able to make this olefin, but you might make it in the wrong place."A mild process that allows chemists to select the olefin's functional form has been a goal for decades. The Rice process took its inspiration from labs that discovered metal catalysts to improve the process and others that studied thermus thermophilus, light-sensitive bacteria that thrive near underwater thermal vents."They have a lot of unusual enzymes," West said. "One of them is called carH, a photoreceptor like a bacterial retina that developed on a parallel evolutionary path to what led to our eyes."CarH incorporates vitamin B12 and cobalt that reacts with light and prompts the formation of an alkene, which in turn alerts the organism to light's presence. "Instead of needing heat and strong bases, it only needs light energy," he said.West said the alkene "is just a byproduct for the bacteria. It doesn't really care. But we thought we could take this cue from nature."The Rice team used B12 and the cobalt it contains with sodium bicarbonate (aka baking soda) as a mild base to make the olefins under blue light at room temperature.A surprise aspect of the research was the appearance of remote elimination, by which they were able to position hydrogen atoms to facilitate further reactions. That could lead to two-step processes for specific products."Basically, we found we could make olefins and not just isolate them," West said. "In the same flask at the same time, we can have a second reaction and turn them into something else. This could be a plug-and-play method where we can start to sub in different molecules."He said the team is working on variations that can be scaled up for industrial production of polypropylene and other plastics based on olefins. "B12 is a little too complicated for commodity-scale synthesis," West said. "But it's great for fine chemicals, and we can buy it from any number of suppliers." | Microbes | 2,020 |
December 8, 2020 | https://www.sciencedaily.com/releases/2020/12/201208142644.htm | Potential antibiotic for drug-resistant pathogen | Scientists from Johns Hopkins University and Medicine have developed a possible new antibiotic for a pathogen that is notoriously resistant to medications and frequently lethal for people with cystic fibrosis and other lung ailments. | The pathogen, called Mycobacterium abscessus, is related to a better-known bacterium that causes tuberculosis and leprosy but has recently emerged as a distinct species presenting most often as a virulent lung infection. The team of scientists from the Krieger School of Arts & Sciences' Department of Chemistry and the School of Medicine's infectious diseases department published their findings in the journal The team has developed one of the first potential treatments of a bacterium that has no FDA-approved treatments and a cure rate less than 50%. Before the compound, called T405, can move closer to becoming a clinical treatment, researchers need to improve its pharmacological potency using a preclinical animal model of the infection."People die of this in our hospitals every week," said Craig Townsend, a professor of chemistry who served as a principal investigator on the study along with Gyanu Lamichhane, an associate professor of medicine. "The data we have is very promising."Despite years of urgent calls for more studies to understand the bacteria and to explore possible treatments, researchers have been wary of experimenting with the most dangerous member of its Non-Tuberculosis Mycobacteria (NTM) family."It's still considered an emerging disease," Lamichhane said. "There are now more NTM than tuberculosis cases in the United States. And this is the most virulent of all of them."The compound T405 has demonstrated a "superior potency against M. abscessus" over two commonly used antibiotics, the paper states. When combined with an existing medication called avibactam, T405 also demonstrated an ability to prevent the bacteria from developing resistance.T405 was also well tolerated in mice and could be administered less than current treatments, exposing patients to fewer toxic side effects such as deafness.People with depressed immune systems and lung diseases are also at risk of developing an infection that is most frequently found in cystic fibrosis patients. Transmission is not well understood, but the bacteria can be found in soil, dust and water. It causes infections in lungs, soft tissue and skin.Current therapeutic guidelines for the infection require 12 to 18 months of multidrug therapy that have resulted in cure rates between 30-50 percent, underscoring the "need for new antibiotics with improved activity," the paper states. | Microbes | 2,020 |
December 8, 2020 | https://www.sciencedaily.com/releases/2020/12/201208111447.htm | Scientists shed new light on how lung bacteria defend against pneumonia | New insight on how bacteria in the lungs protect against invading pathogens has been published today in the open-access | The study in mice shows that a strain of lung bacteria called Lactobacillus provides a barrier against In healthy organisms, 'commensal' bacteria, which live inside the host without harming it, provide a competitive barrier against invading bacterial pathogens. "It is already well known how commensal bacteria in the gut fight off pathogens," explains co-first author Soner Yildiz, Postdoctoral Research Fellow at the University of Geneva, Switzerland. "But how lung bacteria such as Lactobacillus carry out this role is less clear."To address this gap, Yildiz and colleagues studied the role of lung microbiota against Pneumococcus colonisation in mice. The team had previously reported that a significant amount of Lactobacillus bacteria, which are known to act as antimicrobials and immune system modulators, exist in the lung microbiota of healthy mice. In the current study, they identified these commensal bacteria as Lactobacillus murinus (L. murinus), with further gene sequencing and microscopy showing that the bacteria are tightly associated with mouse lung tissue.The team next exposed cultures of L. murinus to Finally, they treated mice with L. murinus following influenza A infection and found that the bacteria provided a barrier against pneumococcal colonisation in the animals."This suggests that resident commensals in the lung could be applied as probiotics to counteract lung colonisation by pathogenic bacteria," concludes senior author Mirco Schmolke, Group Leader at the University of Geneva. "However, further studies are needed before this can be explored as a potential treatment in humans. If it one day proves to be effective, the approach could improve the clinical outcomes for patients who are susceptible to respiratory tract infections." | Microbes | 2,020 |
December 8, 2020 | https://www.sciencedaily.com/releases/2020/12/201208111428.htm | How poor oral hygiene may result in metabolic syndrome | Periodontal or gum disease is known to be a significant risk factor of metabolic syndrome, a group of conditions increasing the risk for heart disease and diabetes. In a new study, researchers from Tokyo Medical and Dental University (TMDU) discovered that infection with Porphyromonas gingivalis, the bacterium causing periodontal disease, causes skeletal muscle metabolic dysfunction, the precursor to metabolic syndrome, by altering the composition of the gut microbiome. | Periodontal bacteria have long been known to cause inflammation within the oral cavity, but also systemically increase inflammatory mediators. As a result, sustained infection with periodontal bacteria can lead to increases in body weight and lead to increased insulin resistance, a hallmark of type 2 diabetes. The function of insulin is to help shuttle glucose from the blood into tissues, most importantly to skeletal muscle, where one quarter of all glucose in stored. Unsurprisingly, insulin resistance plays a key role in the development of metabolic syndrome, a group of conditions including obesity, altered lipid metabolism, high blood pressure, high blood glucose levels, and systemic inflammation. Although skeletal muscle plays a key role in decreasing blood glucose levels, a direct connection between periodontal bacterial infection and the metabolic function of skeletal muscle has not been established yet."Metabolic syndrome has become a widespread health problem in the developed world," says first author of the study Kazuki Watanabe. "The goal of our study was to investigate how periodontal bacterial infection might lead to metabolic alterations in skeletal muscle and thus to the development of metabolic syndrome."To achieve their goal, the researchers first investigated antibody titers to Porphyromonas gingivalis in the blood of patients with metabolic syndrome and found a positive correlation between antibody titers and increased insulin resistance. These results showed that patients with metabolic syndrome were likely to have undergone infection with Porphyromonas gingivalis and thus have mounted an immune response yielding antibodies against the germ. To understand the mechanism behind the clinical observation, the researchers then turned to an animal model. When they gave mice that were fed a high-fat diet (a pre-requisite to developing metabolic syndrome) Porphyromonas gingivalis by mouth, the mice developed increased insulin resistance, and fat infiltration and lower glucose uptake in the skeletal muscle compared with mice that did not receive the bacteria.But how was this bacterium capable of causing systemic inflammation and metabolic syndrome? To answer this question, the researchers focused on the gut microbiome, the network of bacteria present in the gut and with which the organism co-exists symbiotically. Intriguingly, the researchers found that in mice administered with Porphyromonas gingivalis the gut microbiome was significantly altered, which might decrease insulin sensitivity."These are striking results that provide a mechanism underlying the relationship between infection with the periodontal bacterium Porphyromonas gingivalis and the development of metabolic syndrome and metabolic dysfunction in skeletal muscle," says corresponding author of the study Professor Sayaka Katagiri. | Microbes | 2,020 |
December 8, 2020 | https://www.sciencedaily.com/releases/2020/12/201208090008.htm | Magnetic bacteria as micropumps | Cancer drugs have side effects, so for many years, scientists have been exploring ways to transport the active substances to a tumour in the body as precisely as possible. That is the only place that drugs should take effect. One approach is to inject them into the bloodstream and control their transport in small vessels at tumour sites by locally altering the blood flow with tiny vehicles. Research laboratories have created microrobots whose shape and propulsion are inspired by bacteria and that are small enough to be inserted into blood vessels. | These microvehicles can be powered from outside the body by a moving magnetic field.Simone Schürle, Professor at the Department of Health Sciences and Technology, is now going one step further: instead of microrobots inspired by bacteria, she wants to use real bacteria that are magnetic. Researchers discovered such magnetotactic bacteria in the sea 45 years ago. These microorganisms absorb iron dissolved in the water; iron oxide crystals form in their interior and line up in a row. Like a compass needle, these bacteria align themselves with the Earth's magnetic field so they can navigate in the water in a directed manner.ETH Professor Schürle and her team investigated how to use a magnetic field to control these bacteria in the laboratory as a way to direct the flow of liquids in a controlled manner. In their experiments, they applied only relatively weak rotating magnetic fields to spin the bacteria along the desired directions. And with many bacteria in a swarm, it proved possible to move the fluid surrounding them. The bacteria produce an effect similar to that of a micropump, meaning they are able to move active substances present in the fluid in different directions, for example from the bloodstream into the tumour tissue. By using superimposed magnetic fields that locally reinforce or cancel each other out, this pumping activity can be confined to a small region with pinpoint accuracy, as Schürle's team has been able to show in simulations.Moreover, the principle can be put to work outside the body to mix different liquids locally with each other in very small vessels without having to manufacture and control mechanical micropumps."One major advantage of bacteria over microrobots is that they are easy to produce. We can simply cultivate them in bioreactors," Schürle says.Their work is primarily focused on investigating the approach and describing how the bacteria can control the flow. Before such bacteria can be used in the human body, their safety must first be investigated. However, bringing bacteria into the body for medical reasons is an approach that science is already pursuing under the term "living therapeutics," albeit with other types of bacteria, such as E. coli.It should also be possible to use non-natural bacteria for future medical applications. Synthetic biology can be used to construct bacteria that feature optimised functional properties and are safe for use in the human body, for example by not causing allergic reactions. Schürle can envisage treatments using bacteria that are killed before they are introduced into the body as well as treatments using living bacteria.It has also been known for several decades that certain types of anaerobic bacteria (which do not require oxygen to grow) preferably accumulate in cancer patients' tumours. In other words, these bacteria naturally prefer the low oxygen conditions in tumours over the rest of the body. While this was investigated in bacteria other than those used by Schürle's team, synthetic biology could be used to combine the advantages of several bacterial species. This might lead to the development of bacteria that approach the tumour powered by their own flagella (whip-like appendages) and can then be precisely transported deep into the tumour tissue using external magnetic forces. | Microbes | 2,020 |
December 7, 2020 | https://www.sciencedaily.com/releases/2020/12/201207124121.htm | Molecular mechanism of plant immune receptors discovered | In a recent study, Alexander von Humboldt Professor Jijie Chai at the University of Cologne and his team together with MPIPZ researchers have succeeded for the first time in reconstructing the sequence of molecular events that activate an inactive plant immune receptor and thus mediate the death of the host cell. The researchers' discoveries are of great importance for understanding how these critical plant immune molecules protect their hosts from infections. The configuration adopted by the activated protein is similar to that of other plant and mammal receptors, including humans. This suggests that these receptors are based on a common structural principle to trigger intracellular immune signals and cell death in different areas of life. | The scientists describe their results in the article 'Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme' in Although separated by millions of years of evolution, plants and animals have independently developed similar immune strategies to protect themselves against microbial infections. In both kingdoms of life, immune receptors called nucleotide-binding/leucine-rich repeat proteins (NLR proteins) form an important defence layer within cells against pathogen attack. NLRs are complex devices consisting of several modules. These modules recognize the molecules (effectors) of invading microbes. Effectors trigger the immune response of the plant -- they activate receptors, resistance and cell death pathways to limit infection. Based on different structural and signalling characteristics, plant NLRs are divided into two main classes: those that contain coiled-coiled (CC) modules (CNL proteins) and those that contain toll/interleukin-1 receptor/resistance (TIR) modules (TNL proteins).The scientists conducted their research on the model organism Arabidopsis thaliana, or thale cress. Jijie Chai, together with the MPIPZ research group leader Jane Parker and MPIPZ dirctor Paul Schulze-Lefert, determined the structural and biochemical features underlying the activation of a specific receptor: the so-called TNL type NLR Receptor of Peronospora parasitica 1 (RPP1). It protects the model plant against infection with the fungus Hyaloperonospora arabidopsidis (Hpa).To understand how RPP1 protects plants on the molecular level from Hpa infection, the team generated RPP1 protein together with the known Hpa effector ATR1 . The RPP1 receptor activated in this way is an enzyme that breaks down nicotinamide adenine dinucleotide (NAD+), which is important for defence signalling.By isolating RPP1-ATR1 complexes and subjecting them to cryo electron microscopy, the authors have answered two open questions of NLR biology: first, how direct binding of the effector to the NLR receptor induces the activation of a receptor. Secondly, they determined that the TNL receptor in this case organizes itself as a so-called tetramer, a molecule consisting of four tightly packed receptor molecules. Tetramers belong to the group of oligomeric molecules, which are all structurally made up of similar units. The observed tetramer creates a unique surface within a part of the receptor, which is necessary for the cleavage of NAD+ to trigger defence signals.The effector ATR1 induces tetramerization at one end of RPP1 and simultaneously forces the above-mentioned four TIR modules at the opposite end of the molecule to form two asymmetric TIR pairs that degrade NAD+.Strikingly, the results of the groups around Eva Nogales and Brian Staskawicz at the University of California, Berkeley, on another NLR of the TNL type, Roq1 from the tobacco relative Nicotiana benthamiana, also show that TNL activation involves direct effector recognition and adoption of a similar tetrameric structure. The effector recognized by Roq1 is produced by a bacterial pathogen and the activated Roq1 receptor complex provides resistance to bacterial infections. Therefore, the discoveries of Jijie Chai, his team and the MPIPZ researchers seem to be of great importance for understanding how these critical plant immune molecules protect their hosts from infections. More generally, the oligomeric configurations adopted by active RPP1 and Roq1 resemble the induced oligomeric scaffolds of other plant and mammalian NLR receptor proteins, including human innate immune receptors. This suggests that these receptors are based on a common structural principle to trigger intracellular immune signals and cell death in different kingdoms of life. | Microbes | 2,020 |
December 7, 2020 | https://www.sciencedaily.com/releases/2020/12/201207102107.htm | Development of a new method for decoding viral genes | Comprehensive identification of viral proteins encoded by viral genes is required to understand the pathophysiology of viral infections. A research team led by Professor Yasushi Kawaguchi of the Institute of Medical Science, the University of Tokyo, conducted mass spectrometry specialized for novel synthetic proteins of viruses, and developed a new decoding method for viral genes that can easily and quickly obtain even non-canonical genetic information. | Using this new decoding method, they identified nine novel proteins encoded by herpes simplex virus type 1(HSV-1) (*1) and found that one of them, piUL49, is a pathogenic factor that specifically controls the onset of herpes encephalitis (*2).These results were published in It is difficult to decipher the whole picture of diverse and complex genetic information hidden in the viral genome with conventional technology, and the development of a new method has been required for decoding viral genes, especially those encoding non-canonical translational elements.Many viruses are known to shut-off new synthesis of host proteins. Focusing on this property, the research team purified newly synthesized proteins by the BONCAT method (*3) and performed high-sensitivity mass spectrometry.They found that most of the peptides obtained were derived from HSV-1, including peptides from viral proteins encoded by nine novel HSV-1 genes. All the newly identified HSV-1 genes encode non-canonical translational products.They named one of these novel viral proteins piUL49. Using analysis of a mouse model of HSV-1 infection, they clarified that piUL49 is involved in brain-specific viral proliferation and the onset mechanism of viral encephalitis. For details of the research, please see the paper.The entire base sequence of the HSV-1 genome was determined about 20 years ago, and it is thought that the decoding of the viral genes encoding canonical translational elements has already been completed. However, information on the decoding of viral genes encoding non-canonical translational elements has been limited.It is of great academic significance to discover nearly 10 new HSV genes and to clarify that one of them encodes piUL49, which is involved in the development of viral encephalitis.Professor Kawaguchi, the lead scientist of this research, stressed the importance of their finding as follows. "Elucidation of the onset mechanism of encephalitis through piUL49 will greatly contribute to the understanding of the high central nervous system orientation of HSV-1. We hope that the results will lead to the development of new treatments for HSV-1 encephalitis.(*1) Herpes simplex virus type 1 (HSV-1) Herpes simplex virus type 1 (HSV-1) is a virus that causes a variety of human diseases including encephalitis, keratitis, and mucocutaneous and skin diseases such as herpes labialis, genital herpes, and herpetic whitlow.(*2) Herpes encephalitis Herpes encephalitis is caused by an infection of the brain with HSV. The case fatality rate without treatment is as high as 70% or more. Even with antivirals, 10-15% of patients die. Problems such as serious sequelae have also been pointed out.(*3) BONCAT method BONCAT (BioOrthogonal Non-Canonical Amino acid Tagging) is a tool for tracking protein synthesis on the level of single cells within communities and whole organisms. A method that can concentrate only newly synthesized proteins. This method was first reported in 2006 by Dr. DC. Daniela of the University of California et al. | Microbes | 2,020 |
December 3, 2020 | https://www.sciencedaily.com/releases/2020/12/201203173438.htm | Leaf microbiomes are a neighborhood affair in northern forests | Forest leaves are teeming with bacterial life -- but despite the vast extent of bacteria-covered foliage across the world, this habitat, known as the phyllosphere, remains full of mysteries. How do bacteria spread from tree to tree? Do certain types of bacteria only live on certain types of trees? | A new paper published in the Ecological Society of America's journal Geneviève Lajoie, now a post-doctoral researcher at the University of British Columbia and the paper's lead author, performed the research as a Ph.D. student at the Université du Québec à Montréal. She and her field assistant spent a summer in hot pursuit of bacteria-covered foliage, camping at remote parks and rushing to get their leaf samples back to the lab for analysis before new conditions altered the leaves' resident microbes.The team sampled foliage at sites across Québec, Ontario and the northeastern United States. Lajoie's analysis zeroed in on the iconic sugar maple -- a species that is abundant at the southern end of the study range, but tapers off at more northern latitudes where conifers dominate the landscape. In fact, at the northern reaches of the study range, at sites like Monts-Valin National Park, sugar maples become anomalous enough that tracking them down among their evergreen neighbors was a challenge."To reach the site, we drove up north from Québec City and witnessed the gradual transition from the mixed deciduous forest of the Saint Lawrence Valley to a boreal landscape dominated by conifers," Lajoie said. "Going sampling over the next days, we were looking for sugar maple populations -- our focal species. Even though we knew it could be found in the park despite it being the northern limit of its range, encountering these beautiful trees seemingly out of place but still thriving were particularly amazing moments for me."However, despite being outliers on a conifer-dominated landscape, these northernmost sugar maple trees had adopted leaf microbiomes that blended in with their coniferous neighbors. LaJoie found a pattern along the latitudinal gradient of her study area: southern sugar maples, which are surrounded by lots of other sugar maples, tended to share a relatively similar microbiome -- one that was distinct from other tree species in the area. But in more northern areas, where sugar maple trees are few and far between, the species hosted bacterial communities that resembled the microbiomes of other more dominant species.The observations echo similar patterns that have been observed among animal microbiomes. Ground-dwelling animals, for instance, tend to have relatively similar microbiomes, possibly through increased contact with the feces of other animals, while canopy-dwelling animals have gut microbiomes that are less similar to each other.While gut microbiomes are a hot research topic in the human health sciences, the forest phyllosphere remains a study system that is not well understood -- and according to Lajoie, the fields of plant ecology and microbiology have been growing mostly in parallel for many years. This study's findings provide a more complete picture of the plant-microbe relationship: what kinds of bacteria go on which trees, and how this pattern varies depending on how well a tree fits in with the crowd. | Microbes | 2,020 |
December 3, 2020 | https://www.sciencedaily.com/releases/2020/12/201203144223.htm | A plant immune receptor: It takes four to tango | Although separated by millions of years of evolution, plants and animals have independently alighted upon similar innate immune strategies to protect themselves against microbial infection. In both kingdoms of life, immune receptors called nucleotide-binding/leucine-rich-repeat (NLR) proteins form an important layer of defence inside cells against pathogen attack. NLRs are complex devices made up of several modules that recognize molecules from invading microbes termed effectors, and then locally activate resistance and cell death pathways to limit infection. Based on distinct structural and signalling features, plant NLRs are divided into two main classes: those that contain coiled-coiled (CC) modules (CNL proteins) and those that harbour Toll/interleukin-1 receptor/resistance (TIR) modules (TNL proteins). In a recent study, MPIPZ researchers and Humboldt Professor Jijie Chai and his team succeeded for the first time in piecing together the sequence of molecular events that convert an inactive TNL-type plant immune receptor into an active 'resistosome' complex that mediates host cell death. | Chai, who is also affiliated with the University of Cologne, joined forces with research group leader Jane Parker and MPIPZ director Paul Schulze-Lefert to determine the structural and biochemical features underlying activation of the Recognition of Peronospora parasitica 1 (RPP1) TNL-type NLR receptor, which protects the model plant Arabidopsis thaliana from infection by the oomycete pathogen Hyaloperonospora arabidopsidis (Hpa). To understand at a molecular level how RPP1 shields plants from Hpa infection, Chai, Schulze-Lefert, Parker and colleagues expressed RPP1 together with a recognized Hpa effector ATR1 protein in insect cells, a system that allows high levels of protein expression. The ATR1-activated RPP1 receptor is an enzyme that breaks down nicotinamide adenine dinucleotide (NAD+), which is important for defence signalling.By isolating RPP1-ATR1 oligomeric complexes and subjecting them to cryo-electron microscopy, the authors have answered two outstanding questions in NLR biology: how direct effector binding induces the conformational activation of an NLR receptor, and how organization of the TNL receptor oligomer (in this case a tetramer composed of four tightly-packed receptor molecules) creates a unique surface within a portion of the receptor, which is necessary for cleaving NAD+ to initiate defence signalling. Specifically, the tetramerization of RPP1 induced by ATR1 at one end of the receptor complex forces -- at the opposite end -- the four TIR modules to form two asymmetric TIR pairs, which are the sites of NAD+ breakdown. Thus, the RPP1 resistosome functions as a 'holoenzyme', the active form of an enzyme for NAD cleavage.Strikingly, findings from the groups of Eva Nogales and Brian Staskawicz at the University of California, Berkeley, on another TNL-type NLR, Roq1 from the tobacco relative Nicotiana benthamiana, also show that TNL activation involves direct effector recognition and adoption of a similar tetrameric structure. The effector recognized by Roq1 is produced by a bacterial pathogen and the activated Roq1 receptor complex provides resistance to bacterial infection. Thus, the discoveries of the MPIPZ researchers seem to have a broad relevance for understanding how these critical plant immune molecules protect their hosts from infection. More generally, the oligomeric configurations adopted by active RPP1 and Roq1 resemble induced oligomeric scaffolds of other plant and mammalian NLR receptor proteins, including human receptors of the innate immune system. This suggests that these receptors rely on a common structural principle to initiate intracellular immune signalling and cell death across different kingdoms of life. | Microbes | 2,020 |
December 3, 2020 | https://www.sciencedaily.com/releases/2020/12/201203133902.htm | Gut microbiome snapshot could reveal chemical exposures in children | Researchers at Duke University have completed the most comprehensive study to date on how a class of persistent pollutants called semi-volatile organic compounds (SVOCs) are associated with the gut microbiome in human children. | The results show that certain SVOCs are correlated with the abundance of bacterial and fungal species living in the human digestive tract and may affect them differently, providing a potential mechanism for measuring exposure to a wide variety of these substances. The study also suggests that exposure to toxic halogenated compounds, chemicals containing carbon and a halogen such as chlorine and bromine, may create a niche for bacteria that feed off of them -- bacteria that are not usually found in the human gut."We found bacteria that researchers use for soil bioremediation to remove chlorinated solvents, which is not an organism that you would expect to find in somebody's gut," said Claudia Gunsch, the Theodore Kennedy Professor of Civil and Environmental Engineering at Duke. "The reason it's used in soils is to detoxify and remove chlorines, which suggests that maybe that's also exactly why they're in these guts."The results appear online on October 30 in the journal "We want to understand the impacts of exposure to SVOCs on our gut microbiome and how that translates to positive or negative health outcomes," Gunsch said. "But right now it's a big black box that we don't understand."SVOCs are a broad class of odorless chemicals that are emitted from building materials and consumer products, often slowly evaporating and settling on dust particles and water droplets. Almost everyone in the developed world is exposed regularly to at least some of these compounds, due to their common use in industrial and consumer products.The thought that these chemicals might have effects on the human microbiome and impact health is relatively new, and the research to uncover what these may be and why they occur is still in its infancy. One important line of work is aimed at children because they typically have higher exposure rates, due to spending more time playing on dusty floors where SVOCs accumulate, and because their growing bodies are more susceptible to novel environmental stressors.One avenue for causing turbulence in a growing child's life is through affecting the gut microbiome. Made up of the complex communities of bacteria and fungi growing and living together throughout the human digestive tract, the gut microbiome has been shown to have a clear importance to childhood development as well as adult health. While some studies have already shown that certain SVOCs have an impact on the gut microbiome of children, the chemicals studied are just a tiny fraction of those that people are exposed to."In theory, perturbations in the gut microbiome of children might be associated with long-term health impacts," added Courtney Gardner, assistant professor of civil and environmental engineering at Washington State University, who conducted the study while still a member of Gunsch's laboratory. "But before we can really study any of them for clear causations, we need to get a sense of which SVOC classes seem to be the most negatively associated with microbiome communities."In their first explorative foray into this field, Gunsch, Gardner and their colleagues at Duke measured the levels of dozens of SVOCs circulating in the bodies of almost 80 children between the ages of three and six. They also characterized each of the children's gut microbiome and then looked for relationships between the differences they found and exposures to SVOCs.There wasn't any shortage of data to work with, as the researchers found 29 SVOC compounds in more than 95% of the samples taken. They also found relationships between the compounds present in children's blood or urine and the relative amounts of key microbes, including 61 bacteria and 24 fungi. After working through the various biomarkers and relationships, the researchers came away with two interesting insights.The first was that children with high levels of halogenated SVOCs have some unusual guests in their guts.The researchers also found that while some SVOCs had a negative effect on bacteria in the gut microbiome, others had a positive effect. With more research into exactly how these various chemicals affect the different species of the gut in their own ways, this work may provide the possibility of using a snapshot of the gut's microbial community as a window into what SVOCs a child has been exposed to."It's currently really complicated and expensive to measure what chemicals people have been exposed to if you don't already know what you're looking for," said Gunsch. "By contrast, this is pretty simple. If we could get a reliable snapshot of SVOC exposure just by sequencing a microbiome's genetic signature, we could use that to help us understand more about the health impacts these chemicals have on our children and ourselves." | Microbes | 2,020 |
December 3, 2020 | https://www.sciencedaily.com/releases/2020/12/201203122254.htm | Researchers developed a sequence analysis pipeline for virus discovery | Researchers from the University of Helsinki have developed a novel bioinformatics pipeline called Lazypipe for identifying viruses in host-associated or environmental samples. | The pipeline was developed in close collaboration between virologists and bioinformaticians. The researchers believe they have succeeded to address many challenges typically encountered in viral metagenomics.Previously, the Viral Zoonooses Research Unit, led by Professor Olli Vapalahti, has published two examples of novel and potentially zoonotic viral agents that were identified with Lazypipe from wild animals that can serve as vectors. A new ebolavirus was identified from faeces and organ samples of Mops condylurus bats in Kenya, and a new tick-borne pathogen Alongshan virus from ticks in Northeast Europe."These examples demonstrate the efficacy of Lazypipe data analysis for NGS libraries with very different DNA/RNA backgrounds, ranging from mammalian tissues to pooled and crushed arthropods," says Dr. Teemu Smura.The current Coronavirus pandemic heightens the need to rapidly detect previously unknown viruses in an unbiased way."The detection of SARS-CoV-2 without reference genome demonstrates the utility of Lazypipe for scenarios in which novel zoonotic viral agents emerge and can be quickly detected by NGS sequencing from clinical samples," says Dr. Ravi Kant.In early April, the research group tested libraries of SARS-CoV-2 positive samples with Lazypipe."We confirmed that the pipeline detected SARS-CoV-2 in 9 out of 10 libraries with default settings and without SARS-CoV-2 reference genome," says Dr. Ilja Pljusnin."Lazypipe could play a crucial role in prediction of emerging infectious diseases," adds Assoc. Prof. Tarja Sironen. | Microbes | 2,020 |
December 2, 2020 | https://www.sciencedaily.com/releases/2020/12/201202114525.htm | Research reveals how a fungal infection activates inflammation | Scientists at St. Jude Children's Research Hospital have identified the mechanisms behind inflammasome activation driven by infection with the fungal pathogen Aspergillus fumigatus. Fungal infection, especially with A. fumigatus, is a leading cause of infection-associated deaths in people with compromised immune systems. The work provides clues to a potential therapeutic approach for treating infectious and inflammatory disorders. The findings were published online today in | "Inflammasomes are important sentinels of an organism's innate immune defense system," said corresponding author and founding member of the inflammasome field Thirumala-Devi Kanneganti, Ph.D., of the St. Jude Immunology department. "Our prior work showed that fungal pathogens activate the inflammasome, but the exact mechanism of action for inflammasome engagement was unknown."To understand these mechanisms for A. fumigatus, the scientists looked for pathogen-associated molecular patterns, which can stimulate the innate immune response by activating the inflammasome. The scientists focused on NLRP3, the most-studied inflammasome sensor.The research identified galactosaminogalactan (GAG), a novel fungal pathogen-associated molecular pattern. GAG is essential for A. fumigatus-induced NLRP3 inflammasome activation. The scientists showed that A. fumigatus deficient in GAG fail to induce inflammasome activation. Conversely, over-production of GAG by A. fumigatus increases inflammasome activation.Additionally, inflammasome activation is critical for clearing A. fumigatus infections in animals. The A. fumigatus fungal strain that failed to produce GAG was more virulent in mice, while the strain that over-produced GAG was less virulent.Similarly, inflammasome activation is protective during gut inflammation in a mouse model of colitis, an inflammatory disease. Treatment with purified GAG provided protection against colitis."We showed that protection against this inflammatory disease was dependent on the ability of GAG to induce inflammasome activation," said first author Benoit Briard, Ph.D., formerly of St. Jude Immunology. "These findings demonstrate the mechanism for the therapeutic potential of GAG in inflammatory diseases." | Microbes | 2,020 |
December 2, 2020 | https://www.sciencedaily.com/releases/2020/12/201202114511.htm | Cell membranes in super resolution | Expansion microscopy (ExM) enables the imaging of cells and their components with a spatial resolution far below 200 nanometres. For this purpose, the proteins of the sample under investigation are cross-linked into a swellable polymer. Once the interactions between the molecules have been destroyed, the samples can be expanded many times over with water. This allows detailed insights into their structures. | "This method was previously limited to proteins. In the journal Jürgen Seibel's team has synthesised functionalised sphingolipids, which are an important component of cell membranes. If these lipids are added to cell cultures, they are incorporated into the cell membranes. They can then be marked with a dye and expanded four to ten times in a swellable polymer.The JMU researchers show that this method -- in combination with structured illumination microscopy (SIM) -- makes it possible for the first time to image different membranes and their interactions with proteins with a resolution of 10 to 20 nanometres: cell membranes, the outer and inner cell nuclear membrane and also the membranes of intracellular organelles such as mitochondria.The sphingolipids also integrate highly efficiently into the membranes of bacteria. This means that, for the first time, pathogens such as "With the new super-resolution microscopic methods, we now want to investigate bacterial infection mechanisms and causes of antibiotic resistance. What we learn in the process could possibly be used for improved therapies," says Professor Thomas Rudel, an expert on bacterial infections.The sphingolipids might also integrate into the membrane of viruses. If this is successful, the interactions of corona viruses with cells could be studied for the first time with high resolution light microscopy. | Microbes | 2,020 |
December 1, 2020 | https://www.sciencedaily.com/releases/2020/12/201201124136.htm | Researchers develop customized targeting of bacteria using lysins | Researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have developed a method to produce customisable engineered lysins that can be used to selectively kill bacteria of interest while leaving others unharmed. The discovery presents a promising alternative to antibiotics for treating existing drug-resistant bacteria and bacterial infections without the risk of causing resistance. | Lysins are enzymes produced by bacteriophages to break open the bacteria cells while treating infections, and have demonstrated potential as a novel class of antimicrobials. A major advantage of lysins is that they allow fast and targeted killing against specific bacterium of choice without inducing resistance.The emergence of multidrug-resistant bacteria has left even minor bacterial infections incurable by many existing antibiotics, with at least 700,000 deaths each year due to drug-resistant diseases according to the World Health Organisation.In a paper titled "Engineered Lysins with Customized Lytic Activities Against Enterococci and Staphylococci" recently published in the journal The study reveals how SMART's engineered lysins were able to selectively kill bacteria like Staphylococci, Enterococcus faecalis, while leaving the Enterococcus faecium bacteria of the same genus unharmed. This is the first report of a chimeric lysin that can both target bacteria of multiple genera as well as selectively kill one bacterial species within a genus over another."The human body contains trillions of bacteria, which form the microbiome, and the majority of the bacteria is either harmless or beneficial to us," says AMR Research Scientist and corresponding author of the paper Dr Boon Chong Goh. "What happens when we are on an antibiotic course is that the antibiotics kill all of the bacteria, leaving us vulnerable to a worse re-infection after we have completed the antibiotic course. Since lysins respect the microbiome and only eliminate the bad pathogenic bacteria, they are a very promising alternative for treating bacterial infections."Awarded with the Ignition and Innovation Grants from SMART Innovation Centre, Dr Goh's team has established the foundation of a technology platform by producing the lysins and testing them in vitro, and are in the process of developing a series of techniques to engineer the lysins."Since lysins are essentially proteins, they can be engineered and mass produced," says Ms. Hana Sakina Bte Muhammad Jai, lead author of the paper and Laboratory Assistant under Dr Goh's team at SMART. "Our study clearly shows how modifying these proteins translates to improvements of their specificity and antibacterial activities""In the lab, we have observed that once a small amount of lysin is added, it only takes 30 minutes to completely kill the bacteria making them a very safe and efficient choice for removing unwanted bacteria," says Ms. Linh Chi Dam, the co-first author of the paper and Laboratory Technologist under Dr Goh's team at SMART. "While developments in the production of customised lysins would greatly impact pharmaceutical industries where lysins can be used to treat bacterial infections, skincare and consumer care industries would also benefit by using lysins as a targeted agent to remove unwanted bacteria from their products."The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) programme. The SMART AMR team was also recently awarded the Intra-CREATE Seed Collaboration Grant to investigate lysins targeting Gram-negative bacteria such as, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. | Microbes | 2,020 |
December 1, 2020 | https://www.sciencedaily.com/releases/2020/12/201201084802.htm | Warning signs over effectiveness of HIV 'wonder drug' in sub-Saharan Africa | Dolutegravir, the current first-line treatment for HIV, may not be as effective as hoped in sub-Saharan Africa, suggests new research published on World AIDS Day. The study finds that this so-called 'wonder drug' may be less effective in patients resistant to older drugs. | As HIV copies itself and replicates, it can develop errors, or 'mutations', in its genetic code (its RNA). While a drug may initially be able to supress or even kill the virus, certain mutations can allow the virus to develop resistance to its effects. If a mutated strain begins to spread within a population, it can mean once-effective drugs are no longer able to treat people.HIV treatment usually consists of a cocktail of drugs that includes a type of drug known as a non-nucleoside reverse-transcriptase inhibitor (NNRTI). However, in recent years, HIV has begun to develop resistance to NNRTIs. Between 10% and 15% of patients in much of sub-Saharan Africa are infected by a strain of HIV resistant to these drugs. If a patient is infected with an NNRTI-resistant strain, they are at a two- to three-fold increased risk of the drug regimen failing.In 2019, the World Health Organization began to recommend dolutegravir as the preferred first-line treatment for HIV in most populations. Dolutegravir was dubbed a 'wonder drug' because it was safe, potent and cost-effective and scientists had seen no drug resistance against it in clinical trials. However, there is little data on the success of dolutegravir against circulating strains of HIV in sub-Saharan Africa.In a study published today in The goal of this study was to determine whether drug resistance to efavirenz prior to starting treatment affected treatment success (suppression of the virus in the blood) over the first two years of therapy with both of these two regimens.As expected, the presence of drug resistance substantially reduced the chances of treatment success in people taking efavirenz, successfully suppressing the virus over 96-weeks in 65% of participants compared to 85% of non-resistant individuals. However, unexpectedly, the same pattern was true for individuals taking dolutegravir-based treatments: 66% of those with efavirenz resistance mutations remained suppressed over 96-weeeks compared to 84% of those without the mutations. These relationships held true after accounting for other factors, such as treatment adherence."We fully expected efavirenz to be less effective among patients HIV strains resistant to NNRTIs," said Dr Mark Siedner, faculty member at the Africa Health Research Institute in KwaZulu-Natal, South Africa and Massachusetts General Hospital in Boston, Massachusetts. "What took us completely by surprise was that dolutegravir -- a different class of drug which is generally effective in the face of drug resistance -- would also be less effective in people with these resistant strains."We are working now to tease out if this was due to the virus or the participants -- for instance, if people with resistance are less likely to take their pills regularly. Either way, if this pattern holds true, it could have far reaching impacts on our predictions of long-term treatment control for millions of people taking dolutegravir in the region."Professor Ravi Gupta from the Department of Medicine at the University of Cambridge said: "This a huge concern. Dolutegravir was very much seen as a 'wonder drug', but our study suggests it might not be as effective in a significant number of patients who are resistant to another important class of antiretroviral drugs."The researchers say it is not clear why efavirenz-resistant mutations should affect susceptibility of dolutegravir, though one hypothesis is that integrase inhibitors such as dolutegravir push the virus to replicate and mutate faster, in turn developing resistance to the new drug in an evolutionary arms race. Alternatively, it could be due to poor adherence to treatment regimens, even though the analysis accounted for adherence by two independent methods. Further research is needed to find out why.Professor Gupta added: "What this shows is that we urgently need to prioritise point of care tests to identify people with drug resistance HIV, particularly against efavirenz, and to more closely and accurately monitor treatment adherence. The development of such tests is at an advanced stage, but there a lack of investment from funders and philanthropic donors. We urgently need agencies and individuals to step forward and help support these programmes."In addition, we need to provide widespread access to viral load monitoring so that we can find those who are struggling, get them on more appropriate regimens, and limit the emergence of resistance when patients are failing therapy." | Microbes | 2,020 |
December 1, 2020 | https://www.sciencedaily.com/releases/2020/12/201201084758.htm | New device offers faster way to detect antibiotic-resistant bacteria | Bacterial infections have become one of the biggest health problems worldwide, and a recent study shows that COVID-19 patients have a much greater chance of acquiring secondary bacterial infections, which significantly increases the mortality rate. | Combatting the infections is no easy task, though. When antibiotics are carelessly and excessively prescribed, that leads to the rapid emergence and spread of antibiotic-resistant genes in bacteria -- creating an even larger problem. According to the Centers for Disease Control and Prevention, 2.8 million antibiotic-resistant infections happen in the U.S. each year, and more than 35,000 people die from of them.One factor slowing down the fight against antibiotic-resistant bacteria is the amount of time needed to test for it. The conventional method uses extracted bacteria from a patient and compares lab cultures grown with and without antibiotics, but results can take one to two days, increasing the mortality rate, the length of hospital stay and overall cost of care.Associate Professor Seokheun "Sean" Choi -- a faculty member in the Department of Electrical and Computer Engineering at Binghamton University's Thomas J. Watson College of Engineering and Applied Science -- is researching a faster way to test bacteria for antibiotic resistance."To effectively treat the infections, we need to select the right antibiotics with the exact dose for the appropriate duration," he said. "There's a need to develop an antibiotic-susceptibility testing method and offer effective guidelines to treat these infections."In the past few years, Choi has developed several projects that cross "papertronics" with biology, such as one that developed biobatteries using human sweat.This new research -- titled "A simple, inexpensive, and rapid method to assess antibiotic effectiveness against exoelectrogenic bacteria" and published in November's issue of the journal "We leverage this biochemical event for a new technique to assess the antibiotic effectiveness against bacteria without monitoring the whole bacterial growth," Choi said. "As far as I know, we are the first to demonstrate this technique in a rapid and high-throughput manner by using paper as a substrate."Working with PhD students Yang Gao (who earned his degree in May and is now working as a postdoctoral researcher at the University of Texas at Austin), Jihyun Ryu and Lin Liu, Choi developed a testing device that continuously monitors bacteria's extracellular electron transfer.A medical team would extract a sample from a patient, inoculate the bacteria with various antibiotics over a few hours and then measure the electron transfer rate. A lower rate would mean that the antibiotics are working."The hypothesis is that the antiviral exposure could cause sufficient inhibition to the bacterial electron transfer, so the readout by the device would be sensitive enough to show small variations in the electrical output caused by changes in antibiotic effectiveness," Choi said.The device could provide results about antibiotic resistance in just five hours, which would serve as an important point-of-care diagnostic tool, especially in areas with limited resources.The prototype -- built in part with funding from the National Science Foundation and the U.S. Office of Naval Research -- has eight sensors printed on its paper surface, but that could be extended to 64 or 96 sensors if medical professionals wanted to build other tests into the device.Building on this research, Choi already knows where he and his students would like to go next: "Although many bacteria are energy-producing, some pathogens do not perform extracellular electron transfer and may not be used directly in our platform. However, various chemical compounds can assist the electron transfer from non-electricity-producing bacteria."For instance, | Microbes | 2,020 |
December 1, 2020 | https://www.sciencedaily.com/releases/2020/12/201201084754.htm | 'Anti-antibiotic' allows for use of antibiotics without driving resistance | An inexpensive, FDA-approved drug -- cholestyramine -- taken in conjunction with an antibiotic prevents the antibiotic from driving antimicrobial resistance, according to new research by scientists at Penn State and the University of Michigan. The team's findings appear today (Dec. 1) in the journal | "Antimicrobial resistance is a serious problem that has led to people dying from common bacterial infections," said Andrew Read, Evan Pugh Professor of Biology and Entomology and director of the Huck Institutes of the Life Sciences, Penn State. "Many of our most important antibiotics are failing, and we are beginning to run out of options. We have created a therapy that may help in the fight against antimicrobial resistance, an 'anti-antibiotic' that allows antibiotic treatment without driving the evolution and onward transmission of resistance."According to Valerie Morley, postdoctoral scholar in the Huck Institutes of the Life Sciences, Penn State, an important cause of antibiotic-resistant infections in healthcare settings is vancomycin-resistant [VR] Enterococcus faecium."E. faecium is an opportunistic pathogen that colonizes the human gastrointestinal tract and spreads via fecal-oral transmission," she said. "The bacterium is asymptomatic in the gut but can cause serious infections, such as sepsis and endocarditis, when introduced to sites like the bloodstream or the spinal cord."Morley noted that daptomycin is one of the few remaining antibiotics to treat VR E. faecium infection, yet VR E. faecium is quickly becoming resistant to daptomycin as well. Daptomycin is administered intravenously to treat infections caused by VR E. faecium. The antibiotic is mostly eliminated by the kidneys, but 5-10% of the dose enters the intestines, where it can drive the evolution of resistance.To investigate whether systemic daptomycin treatment does, indeed, drive an increase in daptomycin-resistant VR E. faecium, the team inoculated mice orally with different strains of daptomycin-susceptible VR E. faecium. Beginning one day after inoculation, the researchers gave the mice daily doses of either subcutaneous daptomycin, oral daptomycin or a control mock injection for five days. The team used a range of doses and routes of administration, including those that would be similar to clinical human doses, to maximize the likelihood of observing resistance emergence. Next, they collected fecal samples from the mice to measure the extent of VR E. faecium shedding into the environment and to determine daptomycin susceptibility of the E. faecium bacteria that were present in the feces.The researchers found that only the highest doses of daptomycin consistently reduced fecal VR E. faecium below the level of detection, whereas lower doses resulted in VR E. faecium shedding. From the bacteria that were shed, the team found that one strain acquired a mutation in a gene that had previously been described in association with daptomycin resistance, while another acquired several mutations that had not previously been associated with daptomycin resistance."Our experiments show that daptomycin resistance can emerge in E. faecium that has colonized the GI tract, and that this resistance can arise through a variety of genetic mutations," said Morley.The team also observed that daptomycin-resistant bacteria were shed even when the daptomycin was administered subcutaneously.Finally, the team investigated whether the orally administered adjuvant cholestyramine -- an FDA-approved bile-acid sequestrant -- could reduce daptomycin activity in the GI tract and prevent the emergence of daptomycin-resistant E. faecium in the gut. They found that cholestyramine reduced fecal shedding of daptomycin-resistant VR E. faecium in daptomycin-treated mice by up to 80-fold."We have shown that cholestyramine binds the antibiotic daptomycin and can function as an 'anti-antibiotic' to prevent systemically administered daptomycin from reaching the gut," said Read.Amit Pai, professor and chair of the Department of Clinical Pharmacy, University of Michigan, noted that no new strategies have been developed to reduce antimicrobial resistance beyond the use of combination therapy, the development of vaccines for upper and lower respiratory tract infections and simply reducing the unnecessary use of antibiotics."These are blunt instruments for antimicrobial resistance reduction at the population level but do not readily translate to an intervention that can be used in individuals," said Pai. "Reducing selective antibiotic pressure on bacteria that reside in the colon is a potential individual-level strategy that deserves greater attention."Other Penn State authors on the paper include Derek Sim, senior research assistant; Samantha Olson, undergraduate student; Lindsey Jackson, undergraduate student; Elsa Hansen, assistant research professor; Grace Usher, graduate student; and Scott Showalter, professor of chemistry. Authors from the University of Michigan include Clare Kinnear, postdoctoral research fellow, and Robert Woods, assistant professor of internal medicine.The Penn State Eberly College of Science and the Eberly Family Trust supported this research. | Microbes | 2,020 |
November 30, 2020 | https://www.sciencedaily.com/releases/2020/11/201130131356.htm | Connection between gut bacteria and vitamin D levels | Our gut microbiomes -- the many bacteria, viruses and other microbes living in our digestive tracts -- play important roles in our health and risk for disease in ways that are only beginning to be recognized. | University of California San Diego researchers and collaborators recently demonstrated in older men that the makeup of a person's gut microbiome is linked to their levels of active vitamin D, a hormone important for bone health and immunity.The study, published November 26, 2020 in Vitamin D can take several different forms, but standard blood tests detect only one, an inactive precursor that can be stored by the body. To use vitamin D, the body must metabolize the precursor into an active form."We were surprised to find that microbiome diversity -- the variety of bacteria types in a person's gut -- was closely associated with active vitamin D, but not the precursor form," said senior author Deborah Kado, MD, director of the Osteoporosis Clinic at UC San Diego Health. "Greater gut microbiome diversity is thought to be associated with better health in general."Kado led the study for the National Institute on Aging-funded Osteoporotic Fractures in Men (MrOS) Study Research Group, a large, multi-site effort that started in 2000. She teamed up with Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego, and co-first authors Robert L. Thomas, MD, PhD, fellow in the Division of Endocrinology at UC San Diego School of Medicine, and Serene Lingjing Jiang, graduate student in the Biostatistics Program at Herbert Wertheim School of Public Health and Human Longevity Sciences.Multiple studies have suggested that people with low vitamin D levels are at higher risk for cancer, heart disease, worse COVID-19 infections and other diseases. Yet the largest randomized clinical trial to date, with more than 25,000 adults, concluded that taking vitamin D supplements has no effect on health outcomes, including heart disease, cancer or even bone health."Our study suggests that might be because these studies measured only the precursor form of vitamin D, rather than active hormone," said Kado, who is also professor at UC San Diego School of Medicine and Herbert Wertheim School of Public Health. "Measures of vitamin D formation and breakdown may be better indicators of underlying health issues, and who might best respond to vitamin D supplementation."The team analyzed stool and blood samples contributed by 567 men participating in MrOS. The participants live in six cities around the United States, their mean age was 84 and most reported being in good or excellent health. The researchers used a technique called 16s rRNA sequencing to identify and quantify the types of bacteria in each stool sample based on unique genetic identifiers. They used a method known as LC-MSMS to quantify vitamin D metabolites (the precursor, active hormone and the breakdown product) in each participant's blood serum.In addition to discovering a link between active vitamin D and overall microbiome diversity, the researchers also noted that 12 particular types of bacteria appeared more often in the gut microbiomes of men with lots of active vitamin D. Most of those 12 bacteria produce butyrate, a beneficial fatty acid that helps maintain gut lining health."Gut microbiomes are really complex and vary a lot from person to person," Jiang said. "When we do find associations, they aren't usually as distinct as we found here."Because they live in different regions of the U.S., the men in the study are exposed to differing amounts of sunlight, a source of vitamin D. As expected, men who lived in San Diego, California got the most sun, and they also had the most precursor form of vitamin D.But the team unexpectedly found no correlations between where men lived and their levels of "It seems like it doesn't matter how much vitamin D you get through sunlight or supplementation, nor how much your body can store," Kado said. "It matters how well your body is able to metabolize that into active vitamin D, and maybe that's what clinical trials need to measure in order to get a more accurate picture of the vitamin's role in health.""We often find in medicine that more is not necessarily better," Thomas added. "So in this case, maybe it's not how much vitamin D you supplement with, but how you encourage your body to use it."Kado pointed out that the study relied on a single snapshot in time of the microbes and vitamin D found in participants' blood and stool, and those factors can fluctuate over time depending on a person's environment, diet, sleep habits, medications and more. According to the team, more studies are needed to better understand the part bacteria play in vitamin D metabolism, and to determine whether intervening at the microbiome level could be used to augment current treatments to improve bone and possibly other health outcomes. | Microbes | 2,020 |
November 30, 2020 | https://www.sciencedaily.com/releases/2020/11/201130113532.htm | Gut microbes: a key to normal sleep | With fall and winter holidays coming up, many will be pondering the relationship between food and sleep. Researchers led by Professor Masashi Yanagisawa at the University of Tsukuba in Japan hope they can focus people on the important middlemen in the equation: bacterial microbes in the gut. Their detailed study in mice revealed the extent to which bacteria can change the environment and contents of the intestines, which ultimately impacts behaviors like sleep. | The experiment itself was fairly simple. The researchers gave a group of mice a powerful cocktail of antibiotics for four weeks, which depleted them of intestinal microorganisms. Then, they compared intestinal contents between these mice and control mice who had the same diet. Digestion breaks food down into bits and pieces called metabolites. The research team found significant differences between metabolites in the microbiota-depleted mice and the control mice. As Professor Yanagisawa explains, "we found more than 200 metabolite differences between mouse groups. About 60 normal metabolites were missing in the microbiota-depleted mice, and the others differed in the amount, some more and some less than in the control mice."The team next set out to determine what these metabolites normally do. Using metabolome set enrichment analysis, they found that the biological pathways most affected by the antibiotic treatment were those involved in making neurotransmitters, the molecules that cells in the brain use to communicate with each other. For example, the tryptophan-serotonin pathway was almost totally shut down; the microbiota-depleted mice had more tryptophan than controls, but almost zero serotonin. This shows that without important gut microbes, the mice could not make any serotonin from the tryptophan they were eating. The team also found that the mice were deficient in vitamin B6 metabolites, which accelerate production of the neurotransmitters serotonin and dopamine.The team also analyzed how the mice slept by looking at brain activity in EEGs. They found that compared with the control mice, the microbiota-depleted mice had more REM and non-REM sleep at night -- when mice are supposed to be active -- and less non-REM sleep during the day -- when mice should be mostly sleeping. The number of REM sleep episodes was higher both during the day and at night, whereas the number of non-REM episodes was higher during the day. In other words, the microbiota-depleted mice switched between sleep/wake stages more frequently than the controls.Professor Yanagisawa speculates that the lack of serotonin was responsible for the sleep abnormalities; however, the exact mechanism still needs to be worked out. "We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep/wake cycles," he says. "Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping."So, this holiday season, when you're feeling sleepy after eating tryptophan-stuffed turkey, please don't forget to thank your gut microbes! | Microbes | 2,020 |
November 30, 2020 | https://www.sciencedaily.com/releases/2020/11/201130091754.htm | Detecting bacteria with fluorescent nanosensors | Researchers from Bochum, Göttingen, Duisburg and Cologne have developed a new method for detecting bacteria and infections. They use fluorescent nanosensors to track down pathogens faster and more easily than with established methods. A team headed by Professor Sebastian Kruß, formerly at Universität Göttingen, now at Ruhr-Universität Bochum (RUB), describes the results in the journal | Traditional methods of detecting bacteria require tissue samples to be taken and analysed. Sebastian Kruß and his team hope to eliminate the need to take samples by using tiny optical sensors to visualise pathogens directly at the site of infection.The sensors are based on modified carbon nanotubes with a diameter of less than one nanometre. If they are irradiated with visible light, they emit light in the near-infrared range (wavelength of 1,000 nanometres and more), which is not visible to humans. The fluorescence behaviour changes when the nanotubes collide with certain molecules in their environment. Since bacteria secrete a characteristic mix of molecules, the light emitted by the sensors can thus indicate the presence of certain pathogens. In the current paper, the research team describes sensors that detect and differentiate harmful pathogens that are associated with, for example, implant infections."The fact that the sensors work in the near-infrared range is particularly relevant for optical imaging, because in this range there are far fewer background signals that can corrupt the results," says Sebastian Kruß, who heads the Functional Interfaces and Biosystems Group at RUB and is a member of the Ruhr Explores Solvation Cluster of Excellence (Resolv). Since light of this wavelength penetrates deeper into human tissue than visible light, this could enable bacteria sensors read out even under wound dressings or on implants."In the future, this could constitute the foundation for optical detection of infections on intelligent implants, as sampling would no longer be required. It would thus allow the healing process or a possible infection to be detected quickly, resulting in improved patient care," says Robert Nißler from the University of Göttingen, lead author of the study. "The possible areas of application are not limited to this," adds Kruß. "For example, improved rapid diagnosis of blood cultures in the context of sepsis is also conceivable in the future." | Microbes | 2,020 |
November 25, 2020 | https://www.sciencedaily.com/releases/2020/11/201125135140.htm | Specific bacterium in the gut linked to irritable bowel syndrome (IBS) | Researchers at the University of Gothenburg have detected a connection between Brachyspira, a genus of bacteria in the intestines, and IBS -- especially the form that causes diarrhea. Although the discovery needs confirmation in larger studies, there is hope that it might lead to new remedies for many people with irritable bowel syndrome. | The pathogenic bacterial genus, Brachyspira, is not usually present in human gut flora. A new study links the bacterium to IBS, particularly the form with diarrhea, and shows that the bacterium hides under the mucus layer protecting the intestinal surface from fecal bacteria.To detect Brachyspira, analyses of fecal samples -- which are routinely used for studying the gut flora -- were insufficient. Instead, the scientists analyzed bacterial proteins in mucus from biopsies taken from the intestine."Unlike most other gut bacteria, Brachyspira is in direct contact with the cells and covers their surface. I was immensely surprised when we kept finding Brachyspira in more and more IBS patients, but not in healthy individuals," says Karolina Sjöberg Jabbar, who gained her doctorate at Sahlgrenska Academy, University of Gothenburg, and is the first author of the article.Globally, between 5 and 10 percent of the adult population have symptoms compatible with IBS (irritable bowel syndrome). The condition causes abdominal pain and diarrhea, constipation, or alternating bouts of diarrhea and constipation. People with mild forms of IBS can often live a fairly normal life, but if the symptoms are more pronounced it may involve a severe deterioration in quality of life."Many questions remain to be answered, but we are hopeful that we might have found a treatable cause of IBS in at least some patients," says Karolina Sjöberg Jabbar.The study was based on colonic tissue samples (biopsies) from 62 patients with IBS and 31 healthy volunteers (controls). Nineteen of the 62 IBS patients (31 percent) proved to have Brachyspira in their gut, but the bacterium was not found in any samples from the healthy volunteers. Brachyspira was particularly common in IBS patients with diarrhea."The study suggests that the bacterium may be found in about a third of individuals with IBS. We want to see whether this can be confirmed in a larger study, and we're also going to investigate whether, and how, Brachyspira causes symptoms in IBS. Our findings may open up completely new opportunities for treating and perhaps even curing some IBS patients, especially those who have diarrhea," says Magnus Simrén, Professor of Gastroenterology at Sahlgrenska Academy, University of Gothenburg, and Senior Consultant at Sahlgrenska University Hospital.In a pilot study that involved treating IBS patients with Brachyspira with antibiotics, the researchers did not succeed in eradicating the bacterium."Brachyspira seemed to be taking refuge inside the intestinal goblet cells, which secrete mucus. This appears to be a previously unknown way for bacteria to survive antibiotics, which could hopefully improve our understanding of other infections that are difficult to treat," Sjöberg Jabbar says.However, if the association between Brachyspira and IBS symptoms can be confirmed in more extensive studies, other antibiotic regimens, as well as probiotics, may become possible treatments in the future. Since the study shows that patients with the bacterium have a gut inflammation resembling an allergic reaction, allergy medications or dietary changes may be other potential treatment options. The researchers at the University of Gothenburg plan to investigate this in further studies."This is another good example of the importance of free, independent basic research that, in cooperation with healthcare, results in unexpected and important discoveries that may be beneficial to many patients. All made without the primary purpose of the study being to look for Brachyspira," says Professor Gunnar C Hansson, who is a world leading authority in research on the protective mucus layer in the intestines.The study is published in the journal | Microbes | 2,020 |
November 25, 2020 | https://www.sciencedaily.com/releases/2020/11/201125122333.htm | New study explains important cause of fatal influenza | It is largely unknown why influenza infections lead to an increased risk of bacterial pneumonia. Researchers at Karolinska Institutet in Sweden have now described important findings leading to so-called superinfections, which claim many lives around the world every year. The study is published in the journal | The Spanish Flu was an influenza pandemic that swept across the world in 1918-20 and unlike many other pandemics disproportionately hit young otherwise healthy adults. One important reason for this was so-called superinfections caused by bacteria, in particular pneumococci.Influenza is caused by a virus, but the most common cause of death is secondary bacterial pneumonia rather than the influenza virus per se. Pneumococcal infections are the most common cause of community-acquired pneumonia and a leading global cause of death. A prior influenza virus infection sensitizes for pneumococcal infections, but mechanisms behind this increase susceptibility are not fully understood. Researchers at Karolinska Institutet have now identified influenza-induced changes in the lower airways that affect the growth of pneumococci in the lungs.Using an animal model, the researchers found that different nutrients and antioxidants, such as vitamin C and other normally cell protective substances leak from the blood, thereby creating an environment in the lungs that favours growth of the bacteria. The bacteria adapt to the inflammatory environment by increasing the production of the bacterial enzyme HtrA.The presence of HtrA weakens the immune system and promotes bacterial growth in the influenza-infected airways. The lack of HtrA stops bacterial growth."The ability of pneumococcus to grow in the lower airways during an influenza infection seems to depend on the nutrient-rich environment with its higher levels of antioxidants that occurs during a viral infection, as well as on the bacteria's ability to adapt to the environment and protect itself from being eradicated by the immune system," says principal investigator Birgitta Henriques Normark, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.The results provide valuable information on how bacteria integrate with their environment in the lungs and could be used to find new therapies for double infections between the influenza virus and pneumococcal bacteria."HtrA is an enzyme, a protease, which helps to weaken the immune system and allows pneumococcal bacteria to penetrate the protective cell layer on the inside of the airways," explains the paper's first author Vicky Sender, researcher at the same department. "A possible strategy can therefore be use of protease inhibitors to prevent pneumococcal growth in the lungs."It is still not known if COVID-19 patients are also sensitive to such secondary bacterial infections, but the researchers think that similar mechanisms could potentially be found in severely ill COVID-19 patients."It's likely that acute lung inflammation, regardless of cause, gives rise to leakage of nutrients and antioxidants, and to an environment that fosters bacterial growth," says Professor Henriques Normark.The study was financed with grants from the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Foundation for Strategic Research, Region Stockholm, the National Technological University (Singapore), the National Research Foundation Fellowship (Singapore), the National University of Singapore, ESCMID, BioMS and the National Medical Research Council. There are no declared conflicts of interest. | Microbes | 2,020 |
November 25, 2020 | https://www.sciencedaily.com/releases/2020/11/201125091459.htm | Research creates hydrogen-producing living droplets, paving way for alternative future energy source | Scientists have built tiny droplet-based microbial factories that produce hydrogen, instead of oxygen, when exposed to daylight in air. | The findings of the international research team based at the University of Bristol and Harbin Institute of Technology in China, are published today in Normally, algal cells fix carbon dioxide and produce oxygen by photosynthesis. The study used sugary droplets packed with living algal cells to generate hydrogen, rather than oxygen, by photosynthesis.Hydrogen is potentially a climate-neutral fuel, offering many possible uses as a future energy source. A major drawback is that making hydrogen involves using a lot of energy, so green alternatives are being sought and this discovery could provide an important step forward.The team, comprising Professor Stephen Mann and Dr Mei Li from Bristol's School of Chemistry together with Professor Xin Huang and colleagues at Harbin Institute of Technology in China, trapped ten thousand or so algal cells in each droplet, which were then crammed together by osmotic compression. By burying the cells deep inside the droplets, oxygen levels fell to a level that switched on special enzymes called hydrogenases that hijacked the normal photosynthetic pathway to produce hydrogen. In this way, around a quarter of a million microbial factories, typically only one-tenth of a millimetre in size, could be prepared in one millilitre of water.To increase the level of hydrogen evolution, the team coated the living micro-reactors with a thin shell of bacteria, which were able to scavenge for oxygen and therefore increase the number of algal cells geared up for hydrogenase activity.Although still at an early stage, the work provides a step towards photobiological green energy development under natural aerobic conditions.Professor Stephen Mann, Co-Director of the Max Planck Bristol Centre for Minimal Biology at Bristol, said: "Using simple droplets as vectors for controlling algal cell organization and photosynthesis in synthetic micro-spaces offers a potentially environmentally benign approach to hydrogen production that we hope to develop in future work."Professor Xin Huang at Harbin Institute of Technology added: "Our methodology is facile and should be capable of scale-up without impairing the viability of the living cells. It also seems flexible; for example, we recently captured large numbers of yeast cells in the droplets and used the microbial reactors for ethanol production." | Microbes | 2,020 |
November 24, 2020 | https://www.sciencedaily.com/releases/2020/11/201124122925.htm | Lung-on-chip provides new insight on body's response to early tuberculosis infection | Scientists have developed a lung-on-chip model to study how the body responds to early tuberculosis (TB) infection, according to findings published today in | TB is a disease caused by the bacterium These findings add to our understanding of what happens during early TB infection, and may explain in part why those who smoke or have compromised surfactant functionality have a higher risk of contracting primary or recurrent infection.TB is one of the world's top infectious killers and affects people of all ages. While it mostly affects adults, there are currently no effective vaccines available to this group. This is partly due to challenges with studying the early stages of infection, which take place when just one or two "We created the lung-on-chip model as a way of studying some of these early events," explains lead author Vivek Thacker, a postdoctoral researcher at the McKinney Lab, École polytechnique fédérale de Lausanne (EPFL), Lausanne, Switzerland. "Previous studies have shown that components of surfactant produced by alveolar epithelial cells can impair bacterial growth, but that the alveolar epithelial cells themselves can allow intracellular bacterial growth. The roles of these cells in early infection are therefore not completely understood."We used our model to observe where the sites of first contact are, how The team used their lung-on-chip model to recreate a deficiency in surfactant produced by alveolar epithelial cells and then see how the lung cells respond to early TB infection. The technology is optically transparent, meaning they could use an imaging technique called time-lapse microscopy to follow the growth of single Their studies revealed that a lack of surfactant results in uncontrolled and rapid bacterial growth in both macrophages and alveolar epithelial cells. On the other hand, the presence of surfactant significantly reduces this growth in both cells and, in some cases, prevents it altogether."Our work shines a light on the early events that take place during TB infection and provides a model for scientists to build on for future research into other respiratory infections," says senior author John McKinney, Head of the Laboratory of Microbiology and Microtechnology at EPFL. "It also paves the way for experiments that increase the complexity of our model to help understand why some TB lesions progress while others heal, which can occur at the same time in the same patient. This knowledge could one day be harnessed to develop effective new interventions against TB and other diseases."The authors add that they are currently using a human lung-on-chip model to study how our lungs may respond to a low-dose infection and inoculation of SARS-CoV-2, the virus that causes COVID-19. | Microbes | 2,020 |
November 24, 2020 | https://www.sciencedaily.com/releases/2020/11/201124092148.htm | Experimental evolution reveals how bacteria gain drug resistance | A research team at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan has succeeded in experimentally evolving the common bacteria | Counteracting multidrug-resistant bacteria is becoming a critical global challenge. It seems that every time we develop new antibiotics, novel antibiotic-resistant bacteria emerge during clinical use. To win this cat-and-mouse game, we must understand how drug resistance evolves in bacteria. Naturally, this process is very complicated, involving numerous changes in genome sequences and cellular states. Therefore, a comprehensive study of resistance dynamics for large numbers of antibiotics has never been reported."Laboratory evolution combined with genomic analyses is a promising approach for understanding antibiotic resistance dynamics," explains Tomoya Maeda, a researcher at RIKEN BDR who led this study. "However, laboratory evolution is highly labor-intensive, requiring serial transfer of cultures over a long period and a large number of parallel experiments." Additionally, Maeda says that identifying the genes that allow resistance to antibiotics is not always easy because of the large number of genetic features that are contained within the data.To overcome these limitations, the team developed an automated robotic culture system that allowed them to successfully perform high-throughput laboratory evolution of "We found that For example, by using this new system, they were able to test 2162 pairs of drug combinations and discovered 157 pairs that have the potential to suppress antibiotic resistance acquisition in | Microbes | 2,020 |
November 24, 2020 | https://www.sciencedaily.com/releases/2020/11/201124092139.htm | Potential treatment against antibiotic-resistant bacteria causing gonorrhea and meningitis | A team from the Institut national de la recherche scientifique (INRS) has demonstrated the effectiveness of an inexpensive molecule to fight antibiotic-resistant strains of the bacteria responsible for gonorrhea and meningococcal meningitis. These two infections affect millions of people worldwide. The results of this research, led by Professor Frédéric Veyrier and Professor Annie Castonguay, have just been published online in the | In recent years, rising rates of antibiotic resistance have been of concern to the World Health Organization (WHO), who has celebrated the World Antimicrobial Awareness Week, from November 18th to 24th 2020. This concern is particularly true in the case of Neisseria gonorrhoeae, for which some strains have developed resistance to all effective antibiotics. This bacterium is responsible for gonorrhea, an infection whose incidence has almost tripled in the last decade in Canada. Resistant strains of Neisseria meningitidis, which cause bacterial meningitis, have also emerged. In the current pandemic context, scientists are particularly concerned about a rise in antibiotic resistance due to their increased use.Unlike other bacteria, Neisseria that cause meningitis and gonorrhea evolve very rapidly because of certain intrinsic properties. For example, they have a great capacity to acquire genes from other bacteria. They also have a suboptimal DNA repair system that leads to mutations; antibiotic resistance can therefore easily emerge. The fact that these diseases affect many people around the world also gives them many opportunities to evolve, explaining why it is urgent to develop new ways to fight these bacteria.The research team has demonstrated the efficacy of a simple molecule in bacterial cultures and in a model of infection. Well known by chemists, this molecule is accessible, inexpensive, and could greatly help in the fight against these two types of pathogenic Neisseria. The advantage of this molecule is its specificity: "We noticed that the molecule only affects pathogenic Neisseria. It does not affect other types of Neisseria that are found in the upper respiratory system and can be beneficial," underlines Professor Frédéric Veyrier, also the scientific manager of the Platform for Characterization of Biological and Synthetic Nanovehicles.During its experiments, the research team tested whether there was any possible resistance to the molecule: "We were able to isolate strains of bacteria that were less sensitive to the treatment, but this resistance was a double-edged sword because these mutants completely lost their virulence" says the microbiologist.For the moment, the team does not know exactly why the molecule reacts specifically with the two types of Neisseria, but they suspect a connection with the membrane of these pathogens. This specificity opens the door to more fundamental research to determine what makes one bacterium virulent compared to others.The next step will be to modify the structure of the molecule to make it more efficient, while maintaining its specificity. In parallel, the team wishes to identify an industrial partner to evaluate the possibility of developing a potential treatment. | Microbes | 2,020 |
November 23, 2020 | https://www.sciencedaily.com/releases/2020/11/201123120702.htm | Social bacteria build shelters using the physics of fingerprints | Forest-dwelling bacteria known for forming slimy swarms that prey on other microbes can also cooperate to construct mushroom-like survival shelters known as fruiting bodies when food is scarce. Now a team at Princeton University has discovered the physics behind how these rod-shaped bacteria, which align in patterns like those on fingerprint whorls and liquid crystal displays, build the layers of these fruiting bodies. The study was published in | "In some ways, these bacteria are teaching us new kinds of physics," said Joshua Shaevitz, professor of physics and the Lewis-Sigler Institute for Integrative Genomics. "These questions exist at the intersection of physics and biology. And you need to understand both to understand these organisms."Myxococcus xanthus, or Myxo for short, is a bacterial species capable of surprisingly cooperative behaviors. For example, large numbers of Myxo cells come together to hunt other bacteria by swarming toward their prey in a single undulating mass.When food is scarce, however, the rod-like cells stack atop one another to form squishy growths called fruiting bodies, which are hideaways in which some of the Myxo cells transform into spores capable of rebooting the population when fresh nutrients arrive. But until now, scientists haven't understood how the rods acquire the ability to begin climbing on top of each other to build the droplet-like structures.To find out more about how these bacteria behave, the researchers set up a microscope capable of tracking Myxo's actions in three dimensions. The scientists recorded videos of the rod-shaped microbes, which pack closely together like stampeding wildebeest, rushing across the microscope dish in swaths that swirl around each other, forming fingerprint-like patterns.When two swaths meet, the researchers observed, the point of intersection was exactly where the new layer of cells started to form. The bacteria started to pile up and created a situation where the only direction to go was up."We found that these bacteria are exploiting particular points of the cell alignment where stresses build that enable the colony to construct new cell layers, one on top of the other," said Ricard Alert, a postdoctoral research fellow in the Princeton Center for Theoretical Science and one of the study's co-first authors. "And that's ultimately how this colony responds to starvation."Researchers call the points where the massing cells collide "topological defects," a term that refers to the mathematics that describe these singular points. Topology is the branch of mathematics that finds similarities between objects such as teacups and donuts, because one can be stretched or deformed into the other."We call these points topological because if you want to get rid of a single one of these defects, you cannot do it by a smooth transformation -- you cannot just perturb the alignment of the cells to get rid of that point where alignment is lost," Alert said. "Topology is about what you can and cannot do via smooth transformations in mathematics."Myxo bacterial cells behave much like liquid crystals, the fluids found in smartphone screens, which are made of rod-shaped molecules. Unlike passive liquid crystals, however, Myxo rods are alive and can crawl. The bacteria most likely have evolved to take advantage of both passive and active factors to build the fruiting bodies, the researchers said.Katherine Copenhagen, associate research scholar in the Lewis-Sigler Institute, and a co-first author on the study, took videos of the cells under the microscope and analyzed the results. She said that at first the team was not sure what they were looking at."We were trying to study layer formation in bacteria to find out how these cells build these droplets, and we had just gotten a new microscope, so I put a sample of the bacteria from another project that had nothing to do with layer formation under the microscope and imaged it for a few hours," Copenhagen said. "The next time our group got together, I said 'I have this video, so let's take a look at it.' And we were mesmerized by what we saw."The combination of physics and biology training among the researchers enabled them to recognize new theoretical insights into how the vertical layers form. "It says something about the value of the collaborative culture at Princeton," said Ned Wingreen, the Howard A. Prior Professor in the Life Sciences, professor of molecular biology and the Lewis-Sigler Institute. "We chat with each other and share crazy ideas and show interesting data to each other.""A moment that I remember quite vividly," Alert said, "is watching these videos at the very beginning of this project and starting to realize, wait, do layers form exactly where the topological defects are? Could it be true?" To explore the results, he followed up the studies by confirming them with numerical and analytical calculations."The initial realization that came just by watching these movies, that was a cool moment," he said. | Microbes | 2,020 |
November 20, 2020 | https://www.sciencedaily.com/releases/2020/11/201120113859.htm | Altered 'coat' disguises fatal brain virus from neutralizing antibodies | A genetic modification in the 'coat' of a brain infection-causing virus may allow it to escape antibodies, according to Penn State College of Medicine researchers. They say testing people for this and other viral mutations may help identify patients at risk for developing a fatal brain disease. | Dr. Aron Lukacher, professor and chair of the Department of Microbiology and Immunology at the College of Medicine, and Susan Hafenstein, professor of medicine and microbiology and immunology at the College of Medicine and professor of biochemistry and molecular biology at Penn State Eberly College of Science, co-led a research team that used high-resolution microscopy to study the capsid, or outer shell of mouse polyomavirus (MuPyV). This virus is a genetic model of JC polyomavirus (JCPyV), which is present and harmless in most people and can cause progressive multifocal leukoencephalopathy (PML), a brain disease, in people taking immunosuppressive therapies.Genetic mutations in the capsid of JCPyV are common in PML patients and scientists have struggled to understand whether they allow the virus to infect brain cells or whether the resulting changes allow the virus to evade elimination by antiviral antibodies and then cause brain infection. Lukacher and Hafenstein studied the mouse equivalent of a common genetic mutation in JC polyomavirus to try and better understand how it may cause PML."Not much is known about how this particular genetic mutation in the JC polyomavirus capsid leads to PML," Lukacher said. "It has been detected in the blood, cerebrospinal fluid and brain tissues of PML patients but not in their urine. This unmutated virus typically sits dormant in the kidneys of healthy people, which got us wondering how this particular mutation contributes to disease progression."The researchers introduced a genetic mutation in the MuPyV capsid similar to one found in JCPyV and conducted a series of experiments to compare outcomes between MuPyV and the altered virus. The virus mutates by swapping out one amino acid, the chemical ingredients used to build the capsid, for another. They found the virus was still able to cause central nervous system infection and hydrocephalus, or brain swelling.To study how the mutation allows the virus to evade antibodies, the research team, including doctoral student Matthew Lauver and medical scientist training program student Daniel Goetschius, used cryogenic electron microscopy to determine the 3D, atomic resolution structure of the virus particles bound to monoclonal antibodies. The results of their analyses were published in the journal The team examined the structural features to see how the monoclonal antibodies recognize the virus capsid and neutralize it. They found that the capsid mutation prevents the monoclonal antibody from being able to interact with the virus, increasing the chances that the virus can infect the brain when patients become immune-suppressed."We studied how other mutations affected MuPyV and found many of them result in impaired kidney and retained brain viral infection," said Lukacher, a Penn State Cancer Institute researcher. "However, only a few of these result in the ability of the virus to evade the immune response."According to Lukacher, more research is needed to determine which JCPyV mutations cause the virus to evade antibodies. He said the goal would be to develop screenings for patients with multiple sclerosis receiving immune-modulating therapies, as well as those immune-compromised by cancers and AIDS, to see who might be at increased risk for developing PML. | Microbes | 2,020 |
November 19, 2020 | https://www.sciencedaily.com/releases/2020/11/201119141753.htm | Insights in the search for new antibiotics | A collaborative research team from the University of Oklahoma, the Memorial Sloan Kettering Cancer Center and Merck & Co. published an opinion article in the journal, | "The rapid spread of antibiotic-resistant bacteria in clinics challenges our modern medicine and the traditional approaches to antibiotic discovery fail to generate new drugs needed for treatment of antibiotic resistant infections," Zgurskaya said. "The current COVID-19 pandemic further magnifies this problem because patients in intensive care units are particularly vulnerable to such infections ... (our) team is working on developing new tools to guide the discovery and optimization of new antibacterial agents."Zgurskaya adds that the increasing frequency of antibiotic resistance has created a significant health care challenge and will progressively worsen without innovative solutions."In particular, Gram-negative pathogens present both biological and chemical challenges that hinder the discovery of new antibacterial drugs," Zgurskaya said. "As a result of these challenges, intensive screening campaigns have led to few successes, highlighting the need for new approaches to identify regions of chemical space that are specifically relevant to antibacterial drug discovery."In the article, the research team provides an overview of emerging insights into this problem and outline a general approach for researchers and scientists to address it."The overall goal is to develop robust cheminformatic tools to predict Gram-negative permeation and efflux, which can then be used to guide medicinal chemistry campaigns and the design of antibacterial discovery libraries," Zgurskaya said.The research was supported with funding from the U.S. Department of Health and Human Services and the National Institutes of Health. The article, Defining new chemical space for drug penetration into Gram-negative bacteria, is available in the November 2020 issue of the academic journal, | Microbes | 2,020 |
November 19, 2020 | https://www.sciencedaily.com/releases/2020/11/201119141732.htm | New effective and safe antifungal isolated from sea squirt microbiome | By combing the ocean for antimicrobials, scientists at the University of Wisconsin-Madison have discovered a new antifungal compound that efficiently targets multi-drug-resistant strains of deadly fungi without toxic side effects in mice. | The new molecule was discovered in the microbiome of a sea squirt from the Florida Keys as part of an effort to identify novel antimicrobials from understudied ecosystems. Scientists named the antifungal turbinmicin, after the sea squirt from which it was isolated, Ecteinascidia turbinate.Disease-causing fungi continue to evolve resistance to the small number of drugs available to thwart them. As a result, more people are dying from previously treatable diseases, such as candidiasis or aspergillosis, which are caused by common fungi that sometimes turn virulent. Identifying compounds like turbinmicin is key to developing new and effective drugs. However, while turbinmicin is a promising drug candidate, additional study of the molecule and extensive preclinical research must be performed before a new drug can become available.A collaboration of chemists, biologists, and physicians from UW-Madison published their findings Nov. 19 in the journal The majority of existing antimicrobials were isolated from soil-dwelling bacteria. As scientists continued probing these bacteria for new drugs, they often turned up the same molecules over and over again."Bacteria in particular are rich sources of molecules. But a lot of the terrestrial ecosystems have been pretty heavily mined for drug discovery," says Tim Bugni, a professor in the UW-Madison School of Pharmacy who led the turbinmicin project. "There's immense bacterial diversity in the marine environment and it's barely been investigated at all."To correct for that oversight, Bugni partnered with UW School of Medicine and Public Health infectious disease professor David Andes, UW-Madison bacteriology professor Cameron Currie, and their colleagues to search neglected ecosystems. Specifically, they sought to discover novel bacteria from marine animals and then screen them for new kinds of antimicrobial compounds.To identify turbinmicin, the research team began by collecting ocean-dwelling invertebrates from the Florida Keys between 2012 and 2016. From these animals, they identified and grew nearly 1,500 strains of actinobacteria, the same group of bacteria that has produced many clinical antibiotics. Using a screening method, they prioritized 174 strains to test against drug-resistant Candida, an increasingly prominent and dangerous disease-causing fungus. Turbinmicin stood out for its effectiveness."Candida auris in particular is pretty nasty," says Bugni. Nearly half of patients with systemic Candida infection die. "The Candida auris strain we targeted in this paper is resistant to all three classes" of existing antifungals.The researchers tested purified turbinmicin against a slate of 39 fungi isolated from patients. These strains both represented diverse species and encompassed all the known ways that fungi have evolved resistance to existing drugs. In lab experiments, turbinmicin halted or killed nearly all fungal strains at low concentrations, indicating a potent effect.Similar experiments in mice infected with drug-resistant strains of Candida auris and Aspergillus fumigatus also demonstrated turbinmicin's ability to attack resistant fungi. Because fungi and animals are closely related, and thus share similar cellular machinery, antifungals can prove toxic to animals as well. Yet, turbinmicin did not show toxic side effects in mice, even at concentrations 1000 times higher than the minimum dose. The effective dose would work out to tens of milligrams for an average-weight adult, less than for many other antibiotics.Based on experiments in yeast led by UW-Madison genetics professor Anjon Audhya, turbinmicin appears to target the cellular packaging and organizational system of fungi. Turbinmicin blocks the action of the protein Sec14p, with the end result that yeast like Candida cannot bud to reproduce. Other kinds of fungi, when exposed to turbinmicin, may have a difficult time shuttling cellular contents around to grow.The researchers have submitted a patent for turbinmicin and have now turned their attention to improving the molecule by making small alterations to its structure that could increase its effectiveness as a drug. The discovery of turbinmicin also serves as a proof-of-concept for the collaboration's efforts to explore new ecosystems and screen thousands of candidates to identify new, effective antimicrobial candidates."Now we have the tools to sort through candidates, find promising strains and produce molecules to do animal studies," says Bugni. "That's the key for targeting multi-drug resistance: you need unique molecules."This work was supported in part by the National Institutes of Health (grants U19 AI109673, U19 AI142720, R35 GM134865, and R01 AI073289). | Microbes | 2,020 |
November 19, 2020 | https://www.sciencedaily.com/releases/2020/11/201119141705.htm | Giant aquatic bacterium is a master of adaptation | The largest freshwater bacterium, Achromatium oxaliferum, is highly flexible in its requirements, as researchers led by the IGB have now discovered: It lives in places that differ extremely in environmental conditions such as hot springs and ice water. The bacterial strains from the different ecosystems do not differ in their gene content, but rather chose what to express. The adaptation is probably achieved by a process which is unique to these bacteria: only relevant genes are enriched in the genomes and transcribed, while others are archived in cell compartments. | Achromatium is special in many respects: It is 30,000 times larger than its "normal" counterparts that live in water and owing to its calcite deposits it is visible to the naked eye. It has several hundred chromosomes, which are most likely not identical. This makes Achromatium the only known bacterium with several different genomes.The researchers have analyzed sequence data bases of sediments and show that Achromatium is universal. It is found in a broad range of environments: in shallow waters as well as in the ocean at a depth of 4000 metres. It can be found in hot springs and ice-cold water; in acidic and alkaline environments as well as in hypersaline waters.Typically, such a wide range of environmental conditions would result in the establishment of new species, well-adapted to their specific environment. However, Achromatium defies this expectation. Though, equipped with equal functionality, the bacteria in the various ecosystems differ in their gene expression patterns by transcribing only relevant genes."We suggest environmental adaptation in Achromatium occurs by increasing the copy number of relevant genes across the cell's hundreds of chromosomes. This is in stark contrast to other bacteria which eventually lose irrelevant genes. So the high number of genomes makes the versatility possible," explains Dr. Danny Ionescu, leader of the study from IGB.Achromatium is full of calcium carbonate crystals that are located between the outer and cytoplasmic membranes. These crystals fold the cytoplasmic membrane forming pockets of cytoplasm which the researchers suggest to hold clusters of chromosomes. They hypothesize that these clusters enable Achromatium to "archive" genes of no immediate use."The functional versatility of Achromatium and its genomic features contradict what we know for other bacteria, for example the concept of bacterial species and the driving forces of bacterial speciation. In Achromatium, mother and daughter cells are likely not identical and each cell is unique holding a multitude of genes, some of which are not essential for life in a particular habitat. Therefore, each cell keeps the potential to rapidly adapt to changing or new environmental conditions," concludes Professor Hans-Peter Grossart, co-author of the study and head of the aquatic microbial ecology group at IGB. | Microbes | 2,020 |
November 19, 2020 | https://www.sciencedaily.com/releases/2020/11/201119124633.htm | Bed dust microorganisms may boost children's health, study suggests | In the most extensive study of its kind, researchers from the University of Copenhagen, in collaboration with the Danish Pediatric Asthma Center at Herlev and Gentofte Hospital, have found a link between microorganisms living in the dust of children's beds and the children's own bacteria. The correlation suggests that microorganisms may reduce a child's risk of developing asthma, allergies and autoimmune diseases later on in life. Invisible to the human eye, our beds are teeming with microbial life. It is life that, especially during early childhood, can affect how microorganisms in our bodies develop, and thereby how resilient we become to various diseases. | To get a better grasp of this relationship, researchers at the University of Copenhagen's Department of Biology and the Danish Pediatric Asthma Center analyzed bed dust samples from the beds of 577 infants before comparing them with respiratory samples from 542 children. It is the largest study of its kind, the aim of which was to determine which environmental factors affected the composition of microorganisms in the bed dust and if there was a correlation between bed dust microorganisms and the bacteria in the children's airways."We see a correlation between the bacteria we find in bed dust and those we find in the children. While they are not the same bacteria, it is an interesting discovery that suggests that these bacteria affect each other. It may prove to have an impact on reducing asthma and allergy risks in later years," explains Professor Søren J. Sørensen of UCPH's Department of Biology.The science was already clear -- a high diversity of microorganisms in the home contributes to the development of a child's resistance to a host of diseases and allergies. Beds can be a central collector of bacteria, microscopic fungi and other microorganisms."We are well aware that microorganisms living within us are important for our health, with regards to asthma and allergies for example, but also for human diseases such as diabetes II and obesity. But to get better at treating these diseases, we need to understand the processes by which microorganisms emerge during our earliest stages of life. And, it seems that the bed plays a role," says Søren J. Sørensen, adding:"Microorganisms in a bed are affected by a dwelling's surroundings, where high bacterial diversity is beneficial. The simple message is that constantly changing bedsheets may not be necessary, but we need to investigate this a bit more closely before being able to say so for sure."A total of 930 different types of bacteria and fungi were found in the dust collected from the beds of the roughly six-month old children. The richness of bacteria depended largely upon the type of dwelling from which the sample was taken from.Researchers studied both rural and urban dwellings. Rural homes had significantly higher levels of bacteria compared to urban apartments."Previous studies inform us that city-dwellers have less diverse gut flora than people who live in more rural settings. This is typically attributed to their spending greater amounts of time outdoors and having more contact with nature. Our studies demonstrate that changes in bacterial flora in bed dust can be an important reason for this difference as well," says Søren J. SørensenFrom previous studies, the researchers also know that pets, older siblings and rural living also contribute to a lowered risk of developing autoimmune diseases.The researchers' next step is to investigate whether the differences in bacterial flora in bed dust can be correlated directly to the development of diseases such as allergies and asthma. | Microbes | 2,020 |
November 19, 2020 | https://www.sciencedaily.com/releases/2020/11/201117113050.htm | Existing UV light technology has potential to reduce COVID-19 transmission indoors | A recent study has shown that a UV light technology already used to prevent the spread of other airborne diseases in buildings has the potential to be effective against Covid-19. | The research, published in the journal UVC is known to be very effective at 'killing', or inactivating, microorganisms however this type of UV light is harmful to humans. Upper room UVGI cleverly uses UVC light to create an irradiation field above the heads of room occupants so it can disinfect the air whilst keeping people within the room safe.The study, led by researchers from Queen Mary University of London and Leeds Beckett University, tested the feasibility of upper room UVGI to reduce Covid-19 transmission by analysing historical published data examining the effect of UV irradiation on coronaviruses. Evaluating all the data, the research team showed that SARS-CoV-2 virus particles found in the air are likely to be susceptible to UVC, and also that the levels of UVC light required to inactivate the virus would be practical and safe for upper room applications.It is now becoming widely accepted that transmission of SARS-CoV-2 virus particles through tiny respiratory droplets, is one of the main ways Covid-19 spreads between people. The risk of airborne transmission is especially high in poorly ventilated buildings and there is an urgent need for technologies to reduce the spread of Covid-19 within these spaces.Professor Clive Beggs, Emeritus Professor of Applied Physiology at Leeds Beckett University, said: "Now we know that Covid-19 infection can occur from airborne exposure to the virus, finding ways to minimise the risk of transmission, particularly in buildings is becoming increasingly important. Whilst we know wearing masks and opening windows are effective ways to minimise the spread of Covid-19 indoors, these measures aren't always practical, especially in winter.""Upper room UVGI is already a well-established technology and has proven effective to prevent the spread of other diseases such as measles and tuberculosis within buildings. This study shows that we have good reason to believe this technology could also protect indoor spaces such as offices, or restaurants and bars, and help to allow us to start to return to 'normal' life in a safe way."Dr Eldad Avital, Reader in Computational (& Experimental) Fluids and Acoustics at Queen Mary, said: "Now it becomes more of an engineering problem of how we can use this technique to prevent the spread in buildings. This is where computational fluid dynamics becomes important as it can start to address questions around how many UVGI lights are needed and where they should be used. One thing we know is particularly important for these systems is air movement, so for them to work effectively in poorly ventilated spaces, you might need to use ceiling fans or other devices to ensure that larger aerosol particles are adequately irradiated."The research team are now focusing their efforts on understanding how UV air disinfection technologies could be put into practice. One project they're currently working on will investigate the use of a low-cost air purifier system to 'disinfect' air based on the UVC technology. "The idea is that air could be taken out of the room using an air purifier and disinfected with UVC light, before the 'clean' air is then put back into the room," said Dr Avital."Another interesting area we're looking into is using ionisers to disinfect the air. These systems release negative ions into the air which latch on to positive ions, such as viruses, making them heavier. This causes them to fall to the ground or onto surfaces, where they can then be removed using normal cleaning approaches." | Microbes | 2,020 |
November 18, 2020 | https://www.sciencedaily.com/releases/2020/11/201118141700.htm | How the polio vaccine virus occasionally becomes dangerous | While the world reels from the spread of SARS-CoV2, the new coronavirus behind COVID-19, a much older and previously feared scourge -- poliovirus -- is close to being completely eradicated. The polio vaccines, developed by Jonas Salk and Albert Sabin in the mid-1950s, heralded the elimination of polio from the U.S., saving countless children from sudden paralysis and death. In the developing world, however, outbreaks of poliovirus still occur sporadically, an ironic consequence of the polio vaccine itself. | The polio vaccine comes in two types: the Salk vaccine, made with a killed virus and the Sabin vaccine, made with a live but weakened, or attenuated, virus. The Sabin vaccine has several advantages for use in the developing world, including the fact that it does not need to be kept cold, and as an oral vaccine, it does not require needles. However, because it contains a live, albeit weakened polio virus, that virus is able to evolve into more virulent forms and cause outbreaks months to years following a vaccination campaign.In a new paper, Adam Lauring, M.D., Ph.D., of the department of microbiology & immunology and the division of infectious disease and a collaborative team describe an enterprising study that allowed them to view the evolution of the vaccine virus into a more dangerous form in real time."Most outbreaks of type 2 polio virus are caused by the vaccine. Then you have a problem where our best weapon is that same vaccine, so you're kind of fighting fire with fire," says Lauring.In an effort to understand the basic biology of poliovirus and how it replicates, Lauring's lab seized an opportunity to build on an earlier study of a new vaccination campaign in semi-rural Bangladesh. This study, which was run by Mami Taniuchi, Ph.D., of the University of Virginia and Michael Famulare, Ph.D,. of the Institute for Disease Modeling in Seattle, Washington, along with a team from the International Centre for Diarrhoeal Disease Research, Bangladesh, followed households where children were vaccinated with the live attenuated virus, collecting weekly stool samples from each household member. The virus within those samples was then genetically analyzed."There's a lot of work being done to try and understand how the virus goes from attenuated to virulent again," says Lauring. "What we haven't known is what it is doing in those first few weeks or months. This was an opportunity to see those early steps."The team was able to confirm three critical mutations that were inferred by previous investigators to be necessary for the virus to become virulent again, identifying for the first time the rate of mutation for those genes from week to week. They also discovered that the attenuated polio virus evolves extremely quick within hosts; much faster than what is typically seen with other viruses over these short timescales."There were a lot of mutations that were being selected because they helped the virus be a better virus," says Lauring. He notes that this could be a critical insight for disease surveillance purposes. Sewage could be analyzed for signs of these types of mutations, serving as an early warning system of a potential outbreak.The work also revealed a spot of good news: while the virus excelled at evolving within a person, those changes were not easily transmitted from person to person."For all the evolution that happens in a person, transmission tends to put a brake on that and really slows things down," says Lauring.Yet every now and then, an enhanced virus makes it to a new host and gains a foothold, triggering disease. The hope, explains Lauring, is that this work will "inform in a better way to tinker with the vaccine so you get fewer downsides and still maintain its upsides -- that it's actually a very effective vaccine." | Microbes | 2,020 |
November 18, 2020 | https://www.sciencedaily.com/releases/2020/11/201118141653.htm | Alzheimer's disease drug may help fight against antibiotic resistance | An experimental Alzheimer's disease treatment is proving effective at treating some of the most persistent, life-threatening antibiotic-resistant bacteria. | Researchers from The University of Queensland, The University of Melbourne and Griffith University have discovered that the drug called PBT2 is effective at disrupting and killing a class of bacteria -- known as Gram-negative bacteria -- that cause infections such as pneumonia, bloodstream infections and meningitis.UQ's Professor Mark Walker said the metal transport drug may offer a last line of defence against some of the world's most difficult to treat superbugs."The emergence of antibiotic-resistant superbugs is an urgent threat to human health, undermining the capacity to treat patients with serious infection," Professor Walker said."Alternative strategies to treat such multi-drug resistant bacteria are urgently needed."Led by UQ's Dr David De Oliveira, our team hypothesised that, by using this experimental Alzheimer's treatment to disrupt the metals inside these bacteria, we would also disrupt their mechanisms of antibiotic resistance."This was shown to be the case, with the Alzheimer's drug -- combined with the antibiotic polymyxin -- successfully tackling antibiotic-resistant superbugs like Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli."Griffith University's Professor Mark von Itzstein AO from the Institute for Glycomics said the new treatment was effective, and offered a range of other benefits."Based on its use as an experimental Alzheimer's treatment, there's been a significant amount of solid science done on this drug already," Professor von Itzstein said."We know, for example, that clinical studies of PBT2 show that it is safe for use in humans."And, given that we've been able to combine it with the antibiotic polymyxin to treat polymyxin-resistant bacteria, we may be able to make other now-ineffective antibiotics become effective again for treating infectious diseases."This could resharpen, so to speak, some of the weapons we thought we'd lost in our fight against antibiotic-resistant bacteria."The University of Melbourne's Associate Professor Christopher McDevitt, from the Peter Doherty Institute for Infection and Immunity (Doherty Institute), said the drug had already proved effective beyond the petri dish."Animal studies show that the combination of polymyxin and PBT2 kills polymyxin-resistant bacteria, completely clearing any infection," Associate Professor McDevitt said."Hopefully in the not-too-distant future people will be able to access this type of treatment in the clinic."New techniques are critical in addressing this building threat to human health, and this treatment is an additional weapon in our arsenal to fight the accelerating threat of antibiotic resistance."If these new solutions aren't developed, it's estimated that by 2050, antimicrobial-resistant bacteria will account for more than 10 million deaths per year."This new treatment could help turn the tide on antibiotic resistance." | Microbes | 2,020 |
November 17, 2020 | https://www.sciencedaily.com/releases/2020/11/201117120722.htm | Microbial remedies target chemical threats in the environment | Across America, hazardous waste sites pose an ongoing threat to human and environmental health. The most severe cases are known as Superfund sites, of which over a thousand currently exist. Some 50 million Americans live within three miles of one of these zones, potentially placing them at increased risk for cancer and other serious diseases. | While decontamination of such sites is a public health priority, the technical challenges are daunting. Of particular concern are a pair of chlorinated chemicals known as TCE and perchlorate. TCE was widely used as a degreasing agent and perchlorate is used in the manufacture of propellants. Due to the widespread reliance on these chemicals in the past and their improper disposal, they have often found their way into the environment, posing significant risks to human health and surrounding ecosystems.Bioremediation for the removal of these highly toxic chemicals, especially when they are present in mixtures, has long been a challenge for scientists. Chlorinated chemicals stubbornly persist in the environment, sometimes contaminating drinking water systems.In a new study, researchers at the Biodesign Swette Center for Environmental Biotechnology explored new ways to rid the environment of these co-occurring toxic chemicals. To accomplish this, Fe0 in combination with microbial cultures containing an unusual microbe known as Dehalococcoides mccartyi were added to soil and groundwater samples from a contaminated Superfund site in Goodyear, Arizona. The contaminated site had formerly been involved in defense and aerospace manufacturing.The researchers describe how Dehalococcoides bacteria can act in synergy with Fe0, known as zero valent iron. The new study describes the conditions under which Fe0, Dehalococcoides, and other bacteria can effectively convert TCE and perchlorate to benign or less toxic end products of microbial biodegradation, (e.g., ethene).The study appears in the current issue of the journal Critically, the technique prevents the TCE degradation reaction from stalling midway through the process. When this happens, a pair of chemicals, cis-DCE and vinyl chloride are produced, instead of ethene. This would be bad news for the environment, as vinyl chloride is recognized as a highly potent carcinogen.Instead, by using low concentrations of aged Fe0 along with Dehalococcoides, a complete reduction of TCE and perchlorate to harmless ethene and chloride ions was achieved. The study also demonstrated that high concentrations of Fe0 inhibited TCE and perchlorate reduction while ferrous iron (Fe2+), an oxidation product of Fe0, significantly slowed down TCE reduction reaction to ethene."Usually, polluted environments contain more than one toxic contaminant, yet, we have limited information for managing environments with multiple contaminants," says Srivatsan Mohana Rangan, lead author of the new study. "The synergies between microbiological and abiotic reactions can help achieve successful remediation of multiple contaminants simultaneously in a shorter timeframe. Our study using microbial cultures with a chemical reductant, zerovalent iron, demonstrates scenarios for successful remediation of TCE and perchlorate, but also underscores scenarios which can exacerbate environmental contamination, by generating carcinogenic chemicals.""We hope this study will help inform remedial design at Phoenix Goodyear Airport North Superfund Site and other contaminated environments where chemical reductants such as Fe0 are used to promote long-term and sustained microbial activities in the soil and groundwater," says Anca Delgado, co-author of the new study. (In addition to her Biodesign appointment, Delgado is an assistant professor at ASU's School of Sustainable Engineering and the Built Environment.)The research findings pave the way for advanced microbial solutions to address contamination by chlorinated chemicals at Superfund sites across the country. | Microbes | 2,020 |
November 17, 2020 | https://www.sciencedaily.com/releases/2020/11/201117113104.htm | Seeking the most effective polymers for personal protective equipment | Personal protective equipment, like face masks and gowns, is generally made of polymers. But not much attention is typically given to the selection of polymers used beyond their physical properties. | To help with the identification of materials that will bind to a virus and speed its inactivation for use in PPE, researchers from the University of Nottingham, EMD Millipore, and the Philipps University of Marburg developed a high-throughput approach for analyzing the interactions between materials and viruslike particles. They report their method in the journal "We've been very interested in the fact that polymers can have effects on cells on their surface," said Morgan Alexander, an author on the paper. "We can get polymers, which resist bacteria, for example, without designing any particular clever or smart material with antibiotic in there. You just have to choose the right polymer. This paper extends this thinking to viral binding."The group created microarrays of 300 different monomer compositions of polymers representing a wide variety of characteristics. They exposed the polymers to Lassa and Rubella viruslike particles -- particles with the same structure as their viral counterparts but without the infectious genomes activated -- to see which materials were able to preferentially adsorb the particles."Knowing that different polymers bind and possibly inactivate virus to different degrees means we may be able to make recommendations. Should I use this existing glove material or that glove if I want the virus to bind to it and die and not fly into the air when I take the gloves off?" Alexander said.Though this may seem like an obvious method for quickly screening large quantities of materials, the team's interdisciplinary makeup makes them uniquely positioned to conduct such a study. The surface scientists have the capabilities to create large numbers of chemicals on microarrays, and the biologists have access to viruslike particles.So far, the tests have only looked at viruslike particles of Lassa and Rubella, but the group is hoping to acquire a grant to look at viruslike particles of SARS-CoV-2, the COVID-19 virus.Once a handful of the best-performing materials have been determined, the next step of the project will be to use live viruses to evaluate the viral infectious lifetime on the materials, taking into account real-world environmental conditions, like humidity and temperature. With enough data, a molecular model can be built to describe the interactions."Strong binding and quick denaturing of a virus on a polymer would be great," said Alexander. "It remains to be seen whether the effect is significantly large to make a real difference, but we need to look to find out." | Microbes | 2,020 |
November 17, 2020 | https://www.sciencedaily.com/releases/2020/11/201117085932.htm | Potential cholera vaccine target discovered | Findings from a team led by investigators at Massachusetts General Hospital (MGH), reported in the online journal mBio, may help scientists develop a more effective vaccine for cholera, a bacterial disease that causes severe diarrhea and dehydration and is usually spread through contaminated water. | The bacterium that causes cholera, called Interestingly, immune responses to the toxin do not protect against cholera, but previous research led by investigator Edward Ryan, MD, director of Global Infectious Diseases at MGH, has shown antibodies that bind "A big question is: How do these antibodies protect? The answer would help develop better vaccines," says Ryan, who is also a professor of Medicine at Harvard Medical School and a professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health. He notes current vaccines for cholera are not very protective in young children, who bear much of the global burden of cholera, and induce relatively short-term protection in recipients.To investigate, Ryan and his colleagues analyzed antibodies recovered from humans who survived cholera. Experiments showed the antibodies block "Our results support a unique mechanism of protection against a human pathogen. We are not aware of previous work demonstrating a comparable direct anti-motility effect of human antibodies," says Ryan. | Microbes | 2,020 |
November 12, 2020 | https://www.sciencedaily.com/releases/2020/11/201112120506.htm | Risk of childhood asthma by Caesarean section is mediated through the early gut microbiome | The prevalence of caesarean section has increased globally in recent decades. While the World Health Organisation suggests that the procedure should be performed in less than 15% of births to prevent morbidity and mortality, the prevalence is higher in most countries. Children born by caesarean section have an increased risk of developing asthma and other immune-mediated diseases compared to children born by vaginal delivery. A link between caesarean section and later disease has been suggested to be mediated through microbial effects. | For the first time, in a new study published in Using the well-established Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort the researchers analyzed the effects of delivery mode on the gut microbiome at multiple timepoints in the first year of life in and to explore whether perturbations of the microbiome can explain the delivery mode-associated risk of developing asthma during childhood.Increased asthma risk was found in children born by caesarean section only if their gut microbiota at age 1 year still carried a caesarean section signature. No associations with asthma existed from the very early though more pronounced microbial perturbations."Even though a child is born by caesarean section and has an immense early microbial perturbation, this may not lead to a higher risk of asthma, if the microbiome matures sufficiently before age 1 year," says Jakob Stokholm, senior researcher and first author on the study.He continues: "Our study proposes the perspective of restoring a caesarean section perturbed microbiome and thereby perhaps prevent asthma development in a child, who is otherwise in high risk. This study provides a mechanism for the known link between C-section birth and heightened risk of asthma: it is a one-two punch-abnormal early microbiota and then failure to mature."Søren J. Sørensen, professor at the University of Copenhagen, adds:"This study has implications for understanding the microbiota's role in asthma development after delivery by caesarean section and could in the future potentially lead to novel prevention strategies and targeted, efficient microbiota manipulation in children who had early perturbations of the microbiome." | Microbes | 2,020 |
November 12, 2020 | https://www.sciencedaily.com/releases/2020/11/201112080906.htm | Connection between household chemicals and gut microbiome | A team of researchers for the first time has found a correlation between the levels of bacteria and fungi in the gastrointestinal tract of children and the amount of common chemicals found in their home environment. | The work, published this month in Courtney Gardner, assistant professor in the Washington State University Department of Civil and Environmental Engineering, is lead author on the paper, which she completed as a postdoctoral researcher in collaboration with Duke University.The gut microbiome, the community of microbes that live in our intestinal tract, has become of increasing interest to researchers in recent years. The microbes in our gut, which include a large variety of bacteria and fungi, are thought to affect many processes, from nutrient absorption to our immunity, and an unhealthy microbiome has been implicated in diseases ranging from obesity to asthma and dementia.In the study, the researchers measured levels of ubiquitous semi-organic compounds in the blood and urine of 69 toddlers and preschoolers and then, using fecal samples, studied the children's gut microbiomes. The semi-volatile organic compounds they measured included phthalates that are used in detergents, plastic clothing such as raincoats, shower curtains, and personal-care products, such as soap, shampoo, and hair spray, as well as per- and polyfluoroalkyl substances (PFASs), which are used in stain- and water-repellent fabrics, coatings for carpets and furniture, nonstick cooking products, polishes, paints, and cleaning products. People are exposed daily to such chemicals in the air and dust in their homes, especially young children who might ingest them by crawling on carpets or frequently putting objects in their mouths.When the researchers looked at the levels of fungi and bacteria in the gut, they found that children who had higher levels of the chemicals in their bloodstream showed differences in their gut microbiome.Children with higher levels of PFASs in their blood had a reduction in the amount and diversity of bacteria, while increased levels of phthalates were associated with a reduction in fungi populations.The correlation between the chemicals and less abundant bacterial organisms was especially pronounced and potentially most concerning, Gardner said."These microbes are perhaps not the main drivers and may have more subtle roles in our biology, but it might be the case that one of these microbes does have a unique function and decreasing its levels may have significant health impacts," she said.The researchers also found, surprisingly, that the children who had high levels of chemical compounds in their blood also had in their gut several types of bacteria that have been used to clean up toxic chemicals. Dehalogenating bacteria have been used for bioremediation to degrade persistent halogenated chemicals like dry cleaning solvents from the environment. These bacteria are not typically found in the human gut."Finding the increased levels of these type of bacteria in the gut means that, potentially, the gut microbiome is trying to correct itself," Gardner said.Gardner hopes to use the information gathered from the study to develop a diagnostic tool for people and perhaps future probiotic interventions to improve health outcomes."While these data do not denote causation, they offer an indication of the types of organisms that may be impacted by exposure to these compounds and provide a springboard for future research," she said. "Gaining a more holistic understanding of the interactions between human-made chemicals, the gut microbiome, and human health is a critical step in advancing public health."The work was funded by the US Environmental Protection Agency and the National Institute of Environmental Health Sciences. | Microbes | 2,020 |
November 11, 2020 | https://www.sciencedaily.com/releases/2020/11/201111144333.htm | Scientists identify protein that protects against Lyme | Yale researchers have discovered a protein that helps protect hosts from infection with the tick-borne spirochete that causes Lyme Disease, a finding that may help diagnose and treat this infection, they report Nov. 11 in the journal | Lyme Disease is the most common vector-borne disease in North America and is transmitted by ticks infected with the spirochete Borrelia burgdorferi. The course of the disease varies among individuals, with the majority experiencing mild symptoms easily treated by antibiotics. However, in some cases of untreated Lyme the infection can spread to the heart, joints, nervous system, and other organs.For the study, the Yale team expressed more than 1,000 human genes in yeast and analyzed their interactions with 36 samples of B. burgdorferi. They found that one protein, Peptidoglycan Recognition Protein 1 (PGLYRP1), acts like an early warning signal to the immune system when exposed to the bacteria. When exposed to the Lyme spirochete, mice lacking PGLYRP1 had much higher levels of B. burgdorferi than mice with the protein and showed signs of immune system dysfunction, the researchers report."Stimulating the ability of people to make more of this protein could help fight infection," said Yale's Erol Fikrig, the Waldemar Von Zedtwitz Professor of Medicine (Infectious Diseases) and professor of epidemiology (microbial diseases) and of microbial pathogenesis and co-corresponding author of the study.Fikrig and his colleagues are also investigating whether people with higher levels of PGLYRP1 may be less susceptible to infection by B. burgdorferi, which would help explain why some infected individuals have better outcomes. | Microbes | 2,020 |
November 9, 2020 | https://www.sciencedaily.com/releases/2020/11/201109124736.htm | Clinicians who prescribe unnecessary antibiotics fuel future antibiotic use | Receiving an initial antibiotic prescription for a viral acute respiratory infection -- the type of infection that doesn't respond to antibiotics -- increases the likelihood that a patient or their spouse will seek care for future such infections and will receive subsequent antibiotic prescriptions, according to the findings of a study from Harvard Medical School and the Harvard T.H. Chan School of Public Health. | The analysis, published online August 10 in The findings are alarming because they suggest that once such prescriptions are given improperly for a viral infection they could become a gateway to more antibiotic use, the researchers said. Overuse of antibiotics is common. Previous studies have shown that nearly a quarter of antibiotics prescribed in an outpatient setting are given inappropriately for a diagnosis that does not warrant antibiotic treatment."The choices physicians make about prescribing antibiotics can have long-term effects on when individual patients choose to obtain care," said lead study author Zhuo Shi, an HMS student in the Harvard-MIT Program in Health Sciences and Technology program. "A physician who prescribes an antibiotic inappropriately needs to understand that it's not just one little prescription of a harmless antibiotic but a potential gateway to a much bigger problem."The researchers used encounter data from a national insurer to analyze more than 200,000 initial visits for acute respiratory infections (ARIs) at 736 urgent care centers across the United States. At those centers, the researchers found that antibiotic prescribing rates for ARIs varied greatly among clinicians. In the highest quartile of prescribers, 80 percent of clinicians prescribed antibiotics for viral respiratory infections, and in the lowest, 42 percent did. To understand the impact of greater antibiotic prescribing, the researchers exploited the fact that patients do not choose their urgent care clinician. They are essentially randomly assigned to a clinician.In the year after an initial ARI visit, patients seen by clinicians in the highest-prescribing group received 14.6 percent more antibiotics for ARI -- an additional three antibiotic prescriptions filled per 100 patients -- compared with patients seen by the lowest-antibiotic-prescribing clinicians. The increase in patient ARI antibiotic prescriptions was largely driven by an increased number of ARI visits, an increase of 5.6 ARI visits per 100 patients, rather than a higher antibiotic prescribing rate during those subsequent ARI visits, the analysis showed.It's not that they were more likely to get antibiotics on repeat visits, the researchers found, simply that each return visit provided another opportunity to receive antibiotics.Why? In the case of a viral illness, patients wrongly attribute improvement in symptoms to the antibiotics. Naturally, next time they have similar symptoms they believe they need more antibiotics, the researchers said."You'll hear lots of people say, 'Every winter I need antibiotics for bronchitis,'" said study senior author Ateev Mehrotra, an associate professor of health care policy in the Blavatnik Institute at Harvard Medical School and a hospitalist at Beth Israel Deaconess Medical Center. "The antibiotics don't actually help, but patients tend to perceive a benefit. The fancy term for this psychological phenomenon is 'illusionary correlation.'""They get antibiotics and they feel better, not because the antibiotics have worked but because the infection has run its course," Mehrotra said. "The next time they become ill with similar symptoms they go back to the doctor to get another prescription."And the lesson isn't just learned by the patients themselves. Their spouses showed similar increases in visits and use of antibiotics for ARIs.The inappropriate use of antibiotics is a serious problem, the researchers said, noting that the practice increases spending unnecessarily, exposes patients to the risk of side effects for no medical reason and helps to drive the rise of antibiotic-resistant strains of bacteria.Using encounter data from a national insurer, the researchers categorized clinicians within each urgent care center based on their ARI antibiotic prescribing rate. The fact that urgent care patients are randomly assigned to a clinician ruled out the possibility that patients might be choosing a physician they knew would likely give them antibiotics for their viral infection, enabling the researchers to examine the impact of physician behavior on future patient behavior. The researchers examined the association between the clinician's antibiotic prescribing rate and the patients' rates of ARI antibiotic receipt as well as their spouses' rate of antibiotic receipt in the subsequent year. Several members of the research team first applied this method to examine pattens of opioid prescribing.While there is plenty of anecdotal evidence that some physicians say they give antibiotics to patients who request them to improve patient satisfaction, the researchers wanted to see whether and how physician prescribing behavior might be fueling the effect. They set out to answer the question: Could an initial prescription from a high-prescribing physician drive future antibiotic-seeking behavior among patients?It does, the analysis showed, and the study, the researchers said, underscores the ongoing need to educate clinicians and patients on judicious prescribing practices to reduce inappropriate prescribing, as well as the overall overuse of antibiotics and its associate risks.Support for this study was provided by the Office of the Director, National Institutes of Health (grant 1DP5OD017897). | Microbes | 2,020 |
November 9, 2020 | https://www.sciencedaily.com/releases/2020/11/201109124730.htm | Key to piercing harmful bacteria's armor | Bacteria are single-celled organisms that are essential to human health, both in our environment and inside our own bodies. However, certain bacterial species can make us sick. | When a physician suspects an illness of bacterial origin, they will perform diagnostic tests to identify what bacterial species is causing disease so that a course of treatment can be devised. One of these tests is called the Gram stain, after Hans Christian Gram, who developed the technique in the 1880s. Gram discovered that certain bacterial species, the so-called "Gram-negative" bacteria, shrug off a purple dye he was using to help visualize the microbes under his microscope. Scientists eventually discovered that Gram-negative bacteria resist dye uptake because they are enveloped in what is, essentially, a microbial suit of armor: their vulnerable cell membrane is protected by a layer of tightly packed sugars called the cell wall, and on top of that, a specialized outer membrane."Understanding how bacteria build this barrier is an important step in engineering strategies to circumvent it," said Thomas Silhavy, the Warner-Lambert Parke-Davis Professor of Molecular Biology, and the senior author on two new papers investigating the outer membrane, one in the journal Proceedings of the National Academy of Sciences and the other in the journal Trends in Microbiology.One of the main components of the outer membrane is a unique molecule called lipopolysaccharide (LPS), which covers the surface of the cell. "LPS helps to increase the mechanical strength of the Gram-negative cell envelope and it also forms a surface coating that prevents toxic molecules, including certain antibiotics, from entering the cell," said Randi Guest, a postdoctoral research associate in the Silhavy lab, a lecturer in molecular biology, and the lead author of the Trends article.LPS is a famously potent toxin that can cause severe illness when it is released from the bacterial outer membrane or secreted by the cell."The amount of LPS produced by the cell is carefully controlled, as too little LPS may lead to cell rupture, while too much LPS, especially if not properly assembled, is toxic," said Guest. "We reviewed studies of three essential membrane proteins that monitor not only LPS biosynthesis inside the cell, but also transport to, and proper assembly at the cell surface."As Guest and colleagues discuss in their article, the construction of the bacterial outer membrane represents a complex problem for bacteria because potentially dangerous LPS, made inside the cell, must be transported across the cell wall to reach the outer membrane. In addition, these processes must be balanced against the manufacture and transport of the other components of the membrane, which in Gram-negative bacteria is mainly made up of a class of molecules called phospholipids."One long-standing mystery in the field is how phospholipids are transported to the outer membrane," said Silhavy. One idea is that phospholipids can flow passively back and forth between the bacterium's inner cell membrane and its outer membrane at zones of contact, but this idea is highly controversial. New research from Silhavy's group provides support for the idea that a passive mode of transport does exist.Jackie Grimm, then a graduate student in Silhavy's lab, together with Handuo Shi, a graduate student in KC Huang's laboratory at Stanford, led an effort to identify proteins involved in trafficking phospholipids between the inner and outer membranes. For their studies, the colleagues used bacteria that have a mutation that increases the rate at which phospholipids flow from the inner membrane to the outer membrane. When they are deprived of nutrients, these bacteria experience shrinkage and rupture of the inner membrane, followed by cell death, because they are unable to make new phospholipids for the inner membrane to replace those lost to the outer membrane. The authors introduced additional mutations into these bacteria, then looked for genes which, when mutated, affect how quickly the bacteria die after nutrient withdrawal."We used next-generation sequencing to screen for genes involved in this process and found that disruption of the gene Although their data indicate that the protein encoded by "This suggests that YhdP might form a hydrophobic channel between the inner and outer membrane through which phospholipids flow," noted Silhavy."Silhavy and colleagues provide the strongest data to date towards identifying how phospholipids are transported between membranes in bacteria, an elusive question for decades in our field," said M. Stephen Trent, Distinguished Professor of Infectious Diseases at the University of Georgia, who was not involved in the work. "They make a strong argument with genetics and biophysics that a protein of unknown function, YhdP, affects a rapid transport process for phospholipids between membranes. It will be really interesting to learn YhdP's role in phospholipid transport in the future." | Microbes | 2,020 |
November 9, 2020 | https://www.sciencedaily.com/releases/2020/11/201109132441.htm | 3D model shows bacterial motor in action | Nagoya University scientists in Japan and colleagues at Yale University in the US have uncovered details of how the bacterial propeller, known as the flagellum, switches between counterclockwise and clockwise rotation, allowing it to control its movement. The findings were published in the journal | To do this, Homma and his colleagues used an advanced imaging technique called cryo-electron tomography, in which images are taken of frozen samples as they are tilted to produce 2D images that are combined to produce a 3D reconstruction. The scientists used samples from two mutant "Our comparative analysis and molecular modelling provide the first structural evidence that the flagellar motor undergoes a profound rearrangement to enable the rotational switch," says Homma.The scientists found that the switch from counterclockwise to clockwise involves a signalling protein, called CheY-P, binding to a protein, called FliM, in the flagellar motor's C-ring. This causes another motor protein, called FliG, to move in a way that exposes charged residues on its surface to a transmembrane protein, called PomA, that forms the stationary part of the motor, called the stator, along with another protein called PomB. The interaction between FliG residues and PomA probably leads to changes in the stator that result in an ion flow generating torque, which ultimately rotates the C-ring."Cryo-electron tomography is rapidly evolving, making it increasingly possible to reveal motor structure at higher resolutions," says Homma. "This current study provides one of the highest resolution images by cryo-electron tomography of the | Microbes | 2,020 |
November 5, 2020 | https://www.sciencedaily.com/releases/2020/11/201105183805.htm | Llama nanobodies could be a powerful weapon against COVID-19 | Today in | These special llama antibodies, called "nanobodies," are much smaller than human antibodies and many times more effective at neutralizing the SARS-CoV-2 virus. They're also much more stable."Nature is our best inventor," said senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. "The technology we developed surveys SARS-CoV-2 neutralizing nanobodies at an unprecedented scale, which allowed us to quickly discover thousands of nanobodies with unrivaled affinity and specificity."To generate these nanobodies, Shi turned to a black llama named Wally -- who resembles and therefore shares his moniker with Shi's black Labrador.Shi and colleagues immunized the llama with a piece of the SARS-CoV-2 spike protein and, after about two months, the animal's immune system produced mature nanobodies against the virus.Using a mass spectrometry-based technique that Shi has been perfecting for the past three years, lead author Yufei Xiang, a research assistant in Shi's lab, identified the nanobodies in Wally's blood that bind to SARS-CoV-2 most strongly.Then, with the help of Pitt's Center for Vaccine Research (CVR), the scientists exposed their nanobodies to live SARS-CoV-2 virus and found that just a fraction of a nanogram could neutralize enough virus to spare a million cells from being infected.These nanobodies represent some of the most effective therapeutic antibody candidates for SARS-CoV-2, hundreds to thousands of times more effective than other llama nanobodies discovered through the same phage display methods used for decades to fish for human monoclonal antibodies.Shi's nanobodies can sit at room temperature for six weeks and tolerate being fashioned into an inhalable mist to deliver antiviral therapy directly into the lungs where they're most needed. Since SARS-CoV-2 is a respiratory virus, the nanobodies could find and latch onto it in the respiratory system, before it even has a chance to do damage.In contrast, traditional SARS-CoV-2 antibodies require an IV, which dilutes the product throughout the body, necessitating a much larger dose and costing patients and insurers around $100,000 per treatment course."Nanobodies could potentially cost much less," said Shi. "They're ideal for addressing the urgency and magnitude of the current crisis."In collaboration with Cheng Zhang, Ph.D., at Pitt, and Dina Schneidman-Duhovny, Ph.D., at the Hebrew University of Jerusalem, the team found that their nanobodies use a variety of mechanisms to block SARS-CoV-2 infection. This makes nanobodies ripe for bioengineering. For instance, nanobodies that bind to different regions on the SARS-CoV-2 virus can be linked together, like a Swiss army knife, in case one part of the virus mutates and becomes drug-resistant."As a virologist, it's incredible to see how harnessing the quirkiness of llama antibody generation can be translated into the creation of a potent nanoweapon against clinical isolates of SARS-CoV-2," said study coauthor and CVR Director Paul Duprex, Ph.D.Additional authors on the study include Sham Nambulli, Ph.D., Zhengyun Xiao, Heng Liu, Ph.D., and Zhe Sang, all of Pitt.Funding for this study was provided by the National Institutes of Health (grants R35GM137905 and R35GM128641), the University of Pittsburgh Clinical and Translational Science Institute, University of Pittsburgh Center for Vaccine Research, and the DSF Charitable Foundation. | Microbes | 2,020 |
November 5, 2020 | https://www.sciencedaily.com/releases/2020/11/201105113029.htm | Resensitizing 'last-resort' antibiotics for treatment of infections | A research team led by Professor Hongzhe SUN, Chair Professor from the Department of Chemistry, Faculty of Science, in collaboration with Dr Pak-Leung HO, Director of the HKU Carol Yu Centre for Infection from the Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU) discovers that by repurposing an antirheumatic gold drug, auranofin (AUR), "last-resort" antibiotics can be resensitized for treatment of infections caused by multidrug-resistant superbugs including bloodstream infections, pneumonia and wound infections. | The findings provide insights into development of inorganic pharmaceutics and new therapeutic approach for superbug infections. The ground-breaking findings on antimicrobial resistance (AMR) are now published in a leading multidisciplinary science journal, Antibiotics are medicines designed to kill bacteria and treat bacterial infections. Antibiotic resistance occurs when bacteria adjust in response to the misuse or overuse of these medicines and it has become one of the biggest public health challenges in this era. At least 2.8 million people get an antibiotic-resistant infection annually in the US, and more than 35,000 people die from it.The most commonly used antibiotics to treat bacterial infections are β-lactams antibiotics, such as cephalosporins and carbapenems. However, their clinical efficacies have been greatly challenged as bacteria produce a resistant determinant that are capable of hydrolysing nearly all β-lactams antibiotics, named metallo-β-lactamases (MBLs). Therefore, the "last-line" antibiotic colistin (COL) has re-emerged as a therapeutic option in response to the outbreak of infections caused by extensively multidrug-resistant Gram-negative pathogens since the mid-1990s. Unfortunately, the efficacy of COL has also been seriously compromised in the regular treatment of lethal bacterial infections, owing to the emergence of another resistant determinant, mobilized colistin resistance (MCR) enzyme in 2015. Owing to the vast structural difference and mode of mechanisms between the two enzymes, it remains an extreme difficulty of adopting a general therapy for infections caused by MBL(s) and MCR(s) co-producing pathogens. As said by Dr Tedros ADHANOM GHEBREYESUS, Director-Genera of World Health Organization (WHO), "As we gather more evidence, we see more clearly and more worryingly how fast we are losing critically important antimicrobial medicines all over the world." Thus, in clinic context, common infections with these "superbugs" may soon be untreatable, which will severely endanger public health system and leave clinicians with virtually no therapeutic options.With little remission from the therapeutic reliance on the current pipeline of β-lactam antibiotics and COL, the combination therapy consisting of an antibiotic resistance and an antibiotic-resistance breaker offers promising options to narrow the gap between multidrug-resistant bacteria and the development of new antibiotics. The research team previously discovered an anti-peptic ulcer bismuth drug, colloidal bismuth subcitrate, potently inhibits MBL activity and re-sensitize MBL-positive bacteria to β-lactam antibiotics. The related works were published in Their new findings follow this widely-recognized discovery, and identifies AUR serves to revive the potency of both carbapenem such as meropenem (MER), and COL through a series of screening on an In the mouse model, combination therapy comprising AUR and COL is highly effective in eradicating multidrug-resistant bacteria in peritonitis infection model. Co-administration with AUR restored the in vivo efficacy of COL, with over 10-fold reduction in MCR-1-producing "Considering the well-recorded safety of in human, AUR as well as related gold drugs as a dual-inhibitor of MBLs and MCRs would largely broaden the therapeutic options in treating the infections caused by multidrug-resistant superbugs," said Professor Sun. | Microbes | 2,020 |
November 3, 2020 | https://www.sciencedaily.com/releases/2020/11/201103115654.htm | Transparent soil-like substances provide window on soil ecology | By using two different transparent soil substitutes, scientists have shown that soil bacteria rely on fungi to help them survive dry periods, says a study published today in | The findings indicate that these soil-like substrates may enable researchers to observe the complex interactions of the myriad microscopic creatures that live in soil. This ability is crucial to help us better understand the role that soil and soil microbes play in healthy ecosystems.Millions of microscopic organisms such as fungi and bacteria live in the soil. They are essential for healthy ecosystems because they support the growth of plants and capture and store carbon from the atmosphere. But studying these processes in real soil can be challenging."To advance the study of soil processes, we used transparent soil substitutes that allowed us to use microscopes and other experimental techniques to see and measure the activity of soil bacteria and determine how this activity depends on the fungi," says lead author Kriti Sharma, who completed the study as a doctoral student at the University of North Carolina at Chapel Hill, US, and is now a postdoctoral scholar at Caltech, Pasadena, US.In the experiments, Sharma and collaborators from Vienna, Austria, successfully grew soil bacteria and fungi in two transparent soil substitutes. One was a synthetic substance called Nafion and the other was a naturally occurring crystal called cryolite. They also demonstrated that it was possible to observe living microbes in these substitutes using a microscope and to measure the organisms' overall metabolic activity and uptake of carbon using a technique called Raman microspectroscopy.Next, they used the soil substitutes to study what happens to bacteria when soil goes from being dried out to wet again. The experiments showed that while many soil bacteria die or become inactive when soil dries out, bacteria living near dead fungi remain active and use the fungi as a source for carbon. "In this way, fungi promote the activity of soil bacteria in changing environmental conditions," Sharma says.The transparent soil systems reported in the study will likely be used by many other researchers who study soil ecology, adds senior author Elizabeth Shank, Associate Professor in the Program in Systems Biology and Department of Microbiology and Physiological Systems at the University of Massachusetts Medical School, Worcester, Massachusetts, US."For example, they could be used to explore how interactions between bacteria, fungi, and other microscopic creatures living in soil help support the growth of crops," she says. "Or to better understand how carbon is stored and released from soil, which may be critical to combating climate change. Overall, these transparent soil substitutes are powerful tools that will help us answer many outstanding questions in soil microbial ecology." | Microbes | 2,020 |
November 3, 2020 | https://www.sciencedaily.com/releases/2020/11/201103104746.htm | A new lead for disarming antibiotic-resistant bacteria | A virus can stop bacteria from sharing genes for antibiotic resistance among themselves, Texas A&M AgriLife researchers have discovered. The results hint at new ways to treat infections and describe a new feature of a highly diverse, largely unexplored part of the biosphere. | The study, published recently in Viruses that only infect bacteria are called bacteriophages, or phages for short. Phages are the most numerous biological entities on Earth. Soil is rife with phages, as is the human gut, and phages that infect and destroy bacteria have found promising uses in combating antibiotic-resistant bacterial infections.Some phages only infect bacteria whose surface contains cylindrical structures called pili. Named after the Latin word pilus, for spear, pili allow bacteria to transfer genes for advantageous traits, such as drug resistance, and enhance bacteria's ability to move and to attack host cells. Because of pili's link to bacterial virulence, researchers have wondered whether new medications could be created to inactivate this feature. While the ways bacteria benefit from pili are clear, how phages use pili to infect bacteria has remained elusive.Zeng's team used fluorescence microscopy to delve into how a phage, MS2, enters an E. coli cell. The researchers created MS2 phages that fluoresce and are fully infectious and stable. The phages attach to pili on E. coli cells, making the pili visible through a fluorescence microscope.Through a series of experiments, Zeng, her graduate student Laith Harb, and the other coauthors obtained a detailed description of what happens when an MS2 phage infects an E. coli.The team discovered that after a phage attaches to a pilus, the pilus retracts, bringing the phage to the bacterial cell surface. The pilus then breaks off behind the phage. Whereas healthy E. coli replenish broken pili, cells infected by MS2 do not. In this way, other phages are prevented from infecting the same cell. The first phage to reach the cell gains a competitive advantage."It's like, 'OK, this cell is mine.' Phages set up their own territory," said Zeng, who is a core faculty member of the Center for Phage Technology, a part of Texas A&M AgriLife Research.Because the phenomenon gives such a boost to the infecting phage, this occurrence may be widespread among other phage strains that employ pili to infect bacteria, Zeng added.The results may be of use in medicine, Zeng said. First, using phages to decrease bacterial virulence may give the immune system time to fight off an infection. Second, the results point to a way of dealing with infections that may be gentler for patients than antibiotics or than using phage therapy to destroy bacteria."One advantage of our method versus traditional phage therapy is that you do not kill the cell, you just disarm it," Zeng said. "Killing the cell may cause a problem, because inside the cell you may have a toxin that could be released into the host."Phages that target pili could also reinforce the action of antibiotics. Some bacterial infections only respond to high doses of antibiotics, which can cause side effects. Adding phages to the mix may allow doctors to decrease the needed antibiotic dosage. | Microbes | 2,020 |
November 2, 2020 | https://www.sciencedaily.com/releases/2020/11/201102120033.htm | Follow your gut: How farms protect from childhood asthma | We are born into an environment full of small organisms called microbiota. Within the first minutes and hours of our lives, they start challenging but also educating our immune system. The largest immune organ is our gut, where maturation of the immune system and maturation of the colonizing bacteria, the gut microbiome, go hand in hand. After profound perturbations in the first year of life, the maturation process, the composition of the gut microbiome gradually stabilizes and accompanies us for our lives. Previous research of the Munich scientists showed an asthma-protective effect by a diverse environmental microbiome, which was particularly pronounced in farm children. The question now was whether this effect could be attributed to the maturation process of the early gut microbiome. | Farm life boosts gut microbiome maturation in children The researchers analyzed fecal samples from more than 700 infants partly growing up on traditional farms between the age of 2 and 12 months who took part in PASTURE -- a European birth cohort, which runs for almost 20 years now with funding from the European Commission."We found that a comparatively large part of the protective farm effect on childhood asthma was mediated by the maturation of the gut microbiome in the first year of life" states Dr. Martin Depner, biostatistician at Helmholtz Zentrum München, and further concludes: "This suggests that farm children are in contact with environmental factors possibly environmental microbiota that interact with the gut microbiome and lead to this protective effect."The researchers anticipated effects of nutrition on the gut microbiome maturation but were surprised to find strong effects of farm-related exposures such as stays in animal sheds. This emphasizes the importance of the environment for the protective effect. In addition, vaginal delivery and breastfeeding fostered a protective microbiome in the first two months of life.Furthermore, the researchers discovered an inverse association of asthma with measured level of fecal butyrate. Butyrate is a short chain fatty acid which is known to have an asthma protective effect in mice. The researchers concluded that gut bacteria such as Roseburia and Coprococcus with the potential of producing short chain fatty acids may contribute to asthma protection in humans as well. Children with a matured gut microbiome showed a higher amount of these bacteria (Roseburia and Coprococcus) compared to other children."Our study provides further evidence that the gut may have an influence on the health of the lung. A mature gut microbiome with a high level of short chain fatty acids had a protective effect on the respiratory health of the children in this study. This suggests the idea of a relevant gut-lung axis in humans," says Dr. Markus Ege, professor for clinical-respiratory epidemiology at the Dr. von Hauner Children's Hospital. "This also means, however, that an immature gut microbiome may contribute to the development of diseases. This emphasizes the need for prevention strategies in the first year of life, when the gut microbiome is highly plastic and amenable to modification."Probiotic prevention strategies The researchers demonstrated that the asthma protective effect is not dependent on one single bacteria only, but on the maturation of the entire gut microbiome. This finding questions the approach of using single bacteria as probiotics for the prevention of asthma. Probiotics should rather be tested with respect to their sustained effect on the compositional structure of the gut microbiome and its maturation early in life.Further studies on cow milk Nutritional aspects analyzed in this study may serve as prevention strategies such as consumption of cow's milk. Unprocessed raw milk, however, cannot be recommended because of the risk of life-threatening infections such as EHEC. Scientists at the Dr. von Hauner Children's Hospital are currently running a clinical trial on the effects of minimally processed but microbiologically safe milk for the prevention of asthma and allergies (MARTHA trial).Helmholtz Zentrum München Helmholtz Zentrum München is a research center with the mission to discover personalized medical solutions for the prevention and therapy of environmentally-induced diseases and promote a healthier society in a rapidly changing world. It investigates important common diseases which develop from the interaction of lifestyle, environmental factors and personal genetic background, focusing particularly on diabetes mellitus, allergies and chronic lung diseases. Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,500 staff members. It is a member of the Helmholtz Association, the largest scientific organization in Germany with more than 40,000 employees at 19 research centers. | Microbes | 2,020 |
November 2, 2020 | https://www.sciencedaily.com/releases/2020/10/201030081545.htm | Hospital floors are hotspot for bacteria, creating route of transfer to patients | The floors of hospital rooms are quickly and frequently contaminated with antibiotic-resistant bacteria within hours of patient admission, creating a route of transfer of potentially dangerous organisms to patients, according to a study published today as part of the proceedings from Decennial 2020: The Sixth International Conference on Healthcare-Associated Infections. Decennial 2020, an initiative of the Centers for Disease Control and Prevention and the Society for Healthcare Epidemiology of America, was cancelled in March due to the pandemic. All abstracts accepted for the meeting have been published as a supplement issue in the journal | "If bacteria stayed on floors this wouldn't matter, but we're seeing clear evidence that these organisms are transferred to patients, despite our current control efforts," said Curtis Donskey, MD, senior author of the study and hospital epidemiologist at the Cleveland VA Medical Center. "Hand hygiene is critical, but we need to develop practical approaches to reduce underappreciated sources of pathogens to protect patients."Researchers with the Northeast Ohio VA Healthcare System closely tracked contamination in hospital rooms of 17 newly admitted patients to identify the timing and route of transfer of bacteria within patients' rooms. Before testing, rooms were thoroughly cleaned and sanitized and all patients screened negative for methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated bacteria. Researchers then observed patients' interactions with healthcare personnel and portable equipment, collecting cultures one-to-three times per day from patients, their socks, beds and other high-touch surfaces, as well as key sections of the floor.Nearly half of rooms tested positive for MRSA within the first 24 hours, and MRSA, C. difficile, and vancomycin-resistant enterococci (VRE) pathogens were identified in 58% of patient rooms within four days of admission. Contamination often started on the floors, but ultimately moved to patients' socks, bedding, and nearby surfaces."While we're showing that these scary sounding bugs can make their way into a patient's room and near them, not everyone who encounters a pathogen will get an infection," said Sarah Redmond, lead author and a medical student at Case Western Reserve University School of Medicine. "With that in mind, are there simple ways to address these areas of exposure without placing too much emphasis on the risk?"In a related study published in August in Researchers noted several limitations of the study, including the small sample size and variables in characteristics among patients and healthcare personnel that may impact how generalizable the study findings are to other hospitals. | Microbes | 2,020 |
October 29, 2020 | https://www.sciencedaily.com/releases/2020/10/201029142017.htm | Face mask aims to deactivate virus to protect others | In the pandemic, people wear face masks to respect and protect others -- not merely to protect themselves, says a team of Northwestern University researchers. | With this in mind, the researchers developed a new concept for a mask that aims to make the wearer less infectious. The central idea, which received support from the National Science Foundation through a RAPID grant, is to modify mask fabrics with anti-viral chemicals that can sanitize exhaled, escaped respiratory droplets.By simulating inhalation, exhalation, coughs and sneezes in the laboratory, the researchers found that non-woven fabrics used in most masks work well to demonstrate the concept. A lint-free wipe with just 19% fiber density, for example, sanitized up to 82% of escaped respiratory droplets by volume. Such fabrics do not make breathing more difficult, and the on-mask chemicals did not detach during simulated inhalation experiments.The research will be published on Oct. 29 in the journal "Masks are perhaps the most important component of the personal protective equipment (PPE) needed to fight a pandemic," said Northwestern's Jiaxing Huang, who led the study. "We quickly realized that a mask not only protects the person wearing it, but much more importantly, it protects others from being exposed to the droplets (and germs) released by the wearer."There seems to be quite some confusion about mask wearing, as some people don't think they need personal protection," Huang added. "Perhaps we should call it public health equipment (PHE) instead of PPE."Huang is a professor of materials science and engineering in Northwestern's McCormick School of Engineering. Graduate student Haiyue Huang and postdoctoral fellow Hun Park, both members of Huang's laboratory, are co-first authors of the paper."Where there is an outbreak of infectious respiratory disease, controlling the source is most effective in preventing viral spread," said Haiyue Huang, a 2020 Ryan Fellowship Awardee. "After they leave the source, respiratory droplets become more diffuse and more difficult to control."Although masks can block or reroute exhaled respiratory droplets, many droplets (and their embedded viruses) still escape. From there, virus-laden droplets can infect another person directly or land on surfaces to indirectly infect others. Huang's team aimed to chemically alter the escape droplets to make the viruses inactivate more quickly.To accomplish this, Huang sought to design a mask fabric that: (1) Would not make breathing more difficult, (2) Can load molecular anti-viral agents such as acid and metal ions that can readily dissolve in escaped droplets, and (3) Do not contain volatile chemicals or easily detachable materials that could be inhaled by the wearer.After performing multiple experiments, Huang and his team selected two well-known antiviral chemicals: phosphoric acid and copper salt. These non-volatile chemicals were appealing because neither can be vaporized and then potentially inhaled. And both create a local chemical environment that is unfavorable for viruses."Virus structures are actually very delicate and 'brittle,'" Huang said. "If any part of the virus malfunctions, then it loses the ability to infect."Huang's team grew a layer of a conducting polymer polyaniline on the surface of the mask fabric fibers. The material adheres strongly to the fibers, acting as reservoirs for acid and copper salts. The researchers found that even loose fabrics with low-fiber packing densities of about 11%, such as medical gauze, still altered 28% of exhaled respiratory droplets by volume. For tighter fabrics, such as lint-free wipes (the type of fabrics typically used in the lab for cleaning), 82% of respiratory droplets were modified.Huang hopes the current work provides a scientific foundation for other researchers, particularly in other parts of the world, to develop their own versions of this chemical modulation strategy and test it further with viral samples or even with patients."Our research has become an open knowledge, and we will love to see more people joining this effort to develop tools for strengthening public health responses," Huang said. "The work is done nearly entirely in lab during campus shutdown. We hope to show researchers in non-biological side of science and engineering and those without many resources or connections that they can also contribute their energy and talent."This work was mainly supported by the National Science Foundation (RAPID DMR-2026944). | Microbes | 2,020 |
October 29, 2020 | https://www.sciencedaily.com/releases/2020/10/201029115809.htm | How the immune system deals with the gut's plethora of microbes | The gut is an unusually noisy place, where hundreds of species of bacteria live alongside whatever microbes happen to have hitched a ride in on your lunch. Scientists have long suspected that the gut's immune system, in the face of so many stimuli, takes an uncharacteristically blunt approach to population control and protection from foreign invaders -- churning out non-specific antibodies with broad mandates to mow the gut's entire microbial lawn without prejudice. | But now, new research published in "It was thought that the gut immune system worked sort of like a general-purpose antibiotic, controlling every bug and pathogen," says Gabriel D. Victora, an immunologist and head of the Laboratory of Lymphocyte Dynamics . "But our new findings tell us that there might be a bit more specificity to this targeting."The research suggests that our immune system may play an active part in shaping the composition of our microbiomes, which are tightly linked to health and disease. "A better understanding of this process could one day lead to major implications for conditions where the microbiome is knocked out of balance," says Daniel Mucida, head of the Laboratory of Mucosal Immunology.When faced with a pathogen, the immune system's B cells enter sites called germinal centers where they "learn" to produce specific antibodies until one B cell emerges, finely-tuned to recognize its target with high efficiency. Dubbed a winner clone, this B cell replicates to generate a mob of cells that produce potent antibodies.Victora, Mucida, and colleagues set out to study how these B cells interact with the melting pot of bacterial species in the gut -- an overabundance of potential targets. Looking at the germinal centers that form in mice intestines, they found that about 1 in 10 of these gut-associated germinal centers had clear winner clones. They then homed in on the winning B cells and found that their antibodies were indeed designed to bind with ever increasing potency to specific species of bacteria living in the gut.The findings show that even in the gut, where millions of microbes wave their thousands of different antigens and vie for the immune system's attention, germinal centers manage to select specific, consistent winners."We can now investigate the winners and look at evolution in germinal centers as an ecological issue involving many different species, as we try to figure out the rules underlying selection in these complex environments," Victora says. "This opens up a whole new area of inquiry." | Microbes | 2,020 |
October 29, 2020 | https://www.sciencedaily.com/releases/2020/10/201029142042.htm | High-sugar diet can damage the gut, intensifying risk for colitis | Mice fed diets high in sugar developed worse colitis, a type of inflammatory bowel disease (IBD), and researchers examining their large intestines found more of the bacteria that can damage the gut's protective mucus layer. | "Colitis is a major public health problem in the U.S. and in other Western countries," says Hasan Zaki, Ph.D., who led the study that appears in today's Colitis can cause persistent diarrhea, abdominal pain, and rectal bleeding. The number of American adults suffering from IBD (which includes Crohn's disease) jumped from 2 million in 1999 to 3 million in 2015, according to the Centers for Disease Control and Prevention. In addition, colitis is beginning to show up in children, who historically did not suffer from it, says Zaki, a UT Southwestern assistant professor of pathology.Because of the disease's much higher prevalence in Western countries, researchers have looked to the Western-style diet -- high in fat, sugar, and animal protein -- as a possible risk factor, says Zaki. While high-fat diets have been found to trigger IBD, the role of sugar has been more controversial, he says.This new study points to sugar -- particularly the glucose found in high fructose corn syrup developed by the food industry in the 1960s and then increasingly used to sweeten soft drinks and other foods -- as a prime suspect. "The incidence of IBD has also increased in Western countries, particularly among children, over this same period," according to the study.UT Southwestern researchers fed mice a solution of water with a 10 percent concentration of various dietary sugars -- glucose, fructose, and sucrose -- for seven days. They found that mice that were either genetically predisposed to develop colitis, or those given a chemical that induces colitis, developed more severe symptoms if they were first given sugar.The researchers then used gene-sequencing techniques to identify the types and prevalence of bacteria found in the large intestines of mice before and after receiving their sugar regimen. After being given sugar treatments for seven days, those fed sucrose, fructose, and -- especially -- glucose showed significant changes in the microbial population inside the gut, according to the study.Bacteria known to produce mucus-degrading enzymes, such as Akkermansia, were found in greater numbers, while some other types of bugs considered good bacteria and commonly found in the gut, such as Lactobacillus, became less abundant.The researchers saw evidence of a thinning of the mucus layer that protects the lining of the large intestine as well as signs of infection by other bacteria. "The mucus layer protects intestinal mucosal tissue from infiltration of gut microbiota," the study explains. "Higher abundance of mucus-degrading bacteria, including Akkermansia muciniphila and Bacteroides fragilis, in glucose-treated mice is, therefore, a potential risk for the intestinal mucus barrier."Due to the erosion of the mucus layer, gut bacteria were in close proximity with the epithelial layer of the large intestine in glucose-treated mice," the study continues. "Breaching of the epithelial barrier is the key initiating event of intestinal inflammation."Although glucose had the greatest effect, "all three simple sugars profoundly altered the composition of gut microbiota," the study reports. Previous studies have shown that gut microbiota of both humans and mice can change rapidly with a change in diet. "Our study clearly shows that you really have to mind your food," says Zaki.After finding changes in the gut microbiota in sugar-fed mice, the researchers fed feces from the sugar-treated mice to other mice. Those mice developed worse colitis, suggesting that glucose-induced susceptibility to colitis can be transmitted along with the destructive intestinal microbiota from affected animals.Zaki says he now plans to study whether and how high sugar intake affects the development of other inflammatory diseases such as obesity, fatty liver disease, and neurodegenerative diseases like Alzheimer's. | Microbes | 2,020 |
October 27, 2020 | https://www.sciencedaily.com/releases/2020/10/201027105424.htm | Drug resistance linked to antibiotic use and patient transfers in hospitals | Understanding the role of antibiotic use patterns and patient transfers in the emergence of drug-resistant microbes is essential to crafting effective prevention strategies, suggests a study published today in | Antimicrobial resistance is a growing global health threat, but preventing it takes smart choices at the local level. The current findings, originally posted on bioRxiv*, provide insights on how antibiotic use patterns and patient transfers in hospitals drive the emergence of resistance, and suggest a new approach for tailoring prevention strategies to an individual hospital or ward."Hospitals continue to be important hotspots for antimicrobial resistance because of the confluence of frequent antibiotic use, fragile patients and the potential for highly resistant pathogens to spread through hospital wards when patients are transferred," explains lead author Julie Shapiro, Postdoctoral Fellow at the CIRI, Centre International de Recherche en Infectiologie, University of Lyon, France.To help hospitals assess the best strategies for preventing the emergence of resistance, Shapiro and her colleagues employed a technique typically used in ecology to study the effect of antibiotic use and patient transfers on infections. They developed a computer model based on a year's worth of data around seven species of infection-causing bacteria, including drug-resistant strains, in 357 hospital wards in France."We found that the volume of antibiotic use at the hospital-ward level had a stronger influence on the incidence of more resistant pathogens, while patient transfers had the most influence on hospital-endemic microbes and those resistant to the last-line antibiotics carbapenems," Shapiro says.They also found that the use of the penicillin antibiotic, piperacillin-tazobactam, was the strongest predictor of the emergence of bacteria that are resistant to the standard treatments for life-threatening blood infections. If this is confirmed in further studies, the authors suggest that the strategy of using piperacillin-tazobactam instead of carbapenems to prevent antimicrobial resistance may need to be reconsidered.In fact, the study showed that the effects of antibiotic prescription and patient transfer patterns on the emergence of drug resistance varied among different microbes and types of infections, suggesting that a more individualised approach to preventing resistance is necessary."Our work highlights the need to tailor strategies against microbial resistance to specific pathogens," concludes senior author Jean-Philippe Rasigade, Associate Professor of Microbiology at the Hospices Civils de Lyon university hospital. "Applying the modelling techniques we used here to other healthcare settings could help inform local and regional antibiotic stewardship and infection control strategies." | Microbes | 2,020 |
October 23, 2020 | https://www.sciencedaily.com/releases/2020/10/201023191037.htm | New imaging method reveals HIV's sugary shield in unprecedented detail | Scientists from Scripps Research and Los Alamos National Laboratory have devised a method for mapping in unprecedented detail the thickets of slippery sugar molecules that help shield HIV from the immune system. | Mapping these shields will give researchers a more complete understanding of why antibodies react to some spots on the virus but not others, and may shape the design of new vaccines that target the most vulnerable and accessible sites on HIV and other viruses.The sugar molecules, or "glycans," are loose and stringy, and function as shields because they are difficult for antibodies to grip and block access to the protein surface. The shields form on the outermost spike proteins of HIV and many other viruses, including SARS-CoV-2, the coronavirus that causes COVID-19, because these viruses have evolved sites on their spike proteins where glycan molecules -- normally abundant in cells -- will automatically attach."We now have a way to capture the full structures of these constantly fluctuating glycan shields, which to a great extent determine where antibodies can and can't bind to a virus such as HIV," says the study's lead author Zachary Berndsen, PhD, a postdoctoral research associate in the structural biology lab of Scripps Research Professor Andrew Ward, PhD.The same wavy flexibility that makes these sugary molecules resistant to antibodies has made them impossible for researchers to capture with traditional atomic-scale imaging. In the new study, which appears in the The Scripps Research team collaborated with the lab of Gnana Gnanakaran, PhD, staff scientist at Los Alamos National Laboratory, which is equipped with high-performance computing resources that enabled fresh approaches for modeling the glycans.The researchers combined an atomic-scale imaging method called cryo-electron microscopy (cryo-EM) with sophisticated computer modeling and a molecule-identifying technique called site-specific mass spectrometry. Cryo-EM relies on averaging tens or hundreds of thousands of individual snapshots to create a clear image, thus highly flexible molecules like glycans will appear only as a blur, if they show up at all.But by integrating cryo-EM with the other technologies, the researchers were able to recover this lost glycan signal and use it to map sites of vulnerability on the surface of Env."This is the first time that cryo-EM has been used along with computational modeling to describe the viral shield structure in atomic detail," says Srirupa Chakraborty, PhD, co-lead author and post-doctoral researcher in the Gnanakaran lab at Los Alamos National Laboratory.The new combined approach revealed the glycans' structure and dynamic nature in extreme detail and helped the team better understand how these complex dynamics affect the features observed in the cryo-EM maps. From this wealth of information, the team observed that individual glycans do not just wiggle around randomly on the spike protein's surface, as once was thought, but instead clump together in tufts and thickets."There are chunks of glycans that seem to move and interact together," Berndsen says. "In between these glycan microdomains is where antibodies apparently have the opportunity to bind."Experimental HIV vaccines rely on modified, lab-made Env proteins to elicit antibody responses. In principle, these vaccines' effectiveness depends in part on the positioning and extent of the shielding glycans on these lab-made viral proteins. Therefore, Berndsen and colleagues applied their method to map the glycans on a modified HIV Env protein, BG505 SOSIP.664, which is used in an HIV vaccine currently being evaluated in clinical trials."We found spots on the surface of this protein that normally would be covered with glycans but weren't -- and that may explain why antibody responses to that site have been noted in vaccination trials," Berndsen says.That finding, and others in the study, showed that Env's glycan shield can vary depending on what type of cell is being used to produce it. In HIV's infections of humans, the virus uses human immune cells as factories to replicate its proteins. But viral proteins used to make vaccines normally are produced in other types of mammalian cells.In another surprise discovery, the team observed that when they used enzymes to slowly remove glycans from HIV Env, the entire protein began to fall apart. Berndsen and colleagues suspect that Env's glycan shield, which has been considered merely a defense against antibodies, may also have a role in managing Env's shape and stability, keeping it poised for infection.The team expect that their new glycan-mapping methods will be particularly useful in the design and development of vaccines -- and not only for HIV. Many of the techniques can be applied directly to other glycan-shielded viruses such as influenza viruses and coronaviruses, and can be extended to certain cancers in which glycans play a key role, the researchers say. | Microbes | 2,020 |
October 22, 2020 | https://www.sciencedaily.com/releases/2020/10/201022125510.htm | Details about broadly neutralizing antibodies provide insights for universal flu vaccine | New research from an immunology team at the University of Chicago may shed light on the challenges of developing a universal flu vaccine that would provide long-lasting and broad protection against influenza viruses. | The study, published October 22 in The research is inspired by the limited efficacy of the annual flu vaccine, which must be adjusted each year to provide the best protection against commonly circulating strains of the virus, and why it so rarely induces broadly neutralizing antibodies."For whatever reason, when we are exposed to the flu virus, the antibody response mounted targets the parts of the virus that want to change, so you have to get vaccinated every year to keep up," said Jenna Guthmiller, PhD, a postdoctoral fellow at the University of Chicago. "But there are some parts of the virus that don't change. So why doesn't the seasonal flu vaccine produce antibodies that target those?"This study has implications for the development of a universal flu vaccine that can elicit broadly neutralizing antibodies and that would only need be administered once or twice during a person's lifetime, instead of every year.These polyreactive antibodies, like all antibodies, are produced by the body's B cells. When a person receives their annual flu vaccine, B cells will bind to the inactivated virus and begin generating antibodies against it, preparing the body to fight off the pathogen if it encounters the live flu virus in the environment.This vaccine-induced immune response tends to produce very specific antibodies that target those frequently-changing epitopes on the surface of the virus, in contrast to broadly neutralizing antibodies that can identify the conserved regions that are the same every year.It's not clear why these polyreactive antibodies aren't produced by the annual vaccine."Our research is trying to understand the features of broadly neutralizing antibodies, and why they're so rarely induced by the seasonal flu vaccine," said Guthmiller. "In this case, we were interested in understanding what gives polyreactive antibodies the ability to bind to multiple antigens, and the implications of that polyreactivity for the overall immune response."The new study found that these polyreactive antibodies tend to bind to the portions of the flu virus that are conserved, and that they are preferentially produced when the body encounters a novel flu strain. Importantly, their unique ability to bind to more than one antigen is potentially due to their flexibility; the antibodies themselves can slightly adjust their conformation, allowing them to imperfectly bind to multiple similarly-shaped antigens.This means that polyreactive antibodies are broadly neutralizing due to their ability to attach to and block the portions of influenza virus that are similar across strains and from year to year. Polyreactive antibodies are therefore ideal candidates for developing a universal flu vaccine -- one that can not only protect against common annual strains, but also novel influenza viruses, like the H1N1 strain seen during the 2009 pandemic.The flexibility and strength of these polyreactive antibodies may make it seem like the ideal immune solution to protect against the flu, so why doesn't the seasonal flu vaccine tend to trigger their production?In the study, the investigators also found that these polyreactive antibodies can sometimes bind to the body's own antigens, causing the polyreactive B cells to be destroyed to avoid an autoimmune response."What we're seeing is that there's this balance. Polyreactivity provides these beneficial features, like broader and better binding, but that comes at the cost of binding to self, which can cause issues," said Guthmiller. "Our seasonal flu vaccine keeps calling back the same specific antibody response because it's effective against these limited strains. To get these broadly neutralizing antibodies, like we'd want in a universal flu vaccine, we'll need something very different, but now we know this has the potential to be self-defeating because of this self-binding."These results speak to the challenge of developing such a vaccine. "We already know it is difficult to target influenza in a universal fashion," said Patrick Wilson, PhD, a professor of medicine at UChicago. "For better or worse, this paper provides important insights into properties of antibodies that can more universally target many influenza strains."The researchers are now working to understand how and why these polyreactive antibodies are self-reactive, and whether or not the immune system actively works to prevent them from being produced. Clarifying their role in the immune response will determine if these polyreactive antibodies can be leveraged safely and effectively and how they might be leveraged to produce a universal influenza vaccine. | Microbes | 2,020 |
October 22, 2020 | https://www.sciencedaily.com/releases/2020/10/201022123113.htm | Are bushmeat hunters aware of zoonotic disease? Yes, but that's not the issue | In the tropics and subtropics, families and communities frequently rely on bushmeat for food security as well as basic income. So, while the harvest and trade of wildlife are illegal in many locales, the practice is commonplace, and with it comes the potential for transmission of a zoonotic disease among human populations. | Even before the emergence of COVID-19, public health experts have been on alert for more information about the attitudes and practices of those who trade in and consume bushmeat. Depending on the wildlife species involved -- baboons, bats, hippopotamus, various monkeys, and more -- hunting, preparing and consuming bushmeat can carry with it the potential to contract and spread diseases such as the widely feared Ebola virus or the more widespread, and perhaps more economically devastating, bacterial infections caused by Escherichia coli (E. coli), Salmonella, Staphylococcus and others. The scientists theorize that if we can help bushmeat traders and consumers keep themselves safe, perhaps we can keep their communities safe, too.To do that, you have to understand the practitioners.A recent paper published in the journal Among their findings, they report that both hunters and, traditionally, the women who cook the meat consider primates to be the most likely wildlife species to carry diseases that humans can catch. Among common zoonotic pathogens, both groups believe that pathogens causing stomach ache or diarrhea and monkeypox can be transmitted by wildlife. Neither the women who cook nor the hunters report being frequently injured during cooking, butchering or hunting, and few report taking precautions while handling bushmeat."Based on responses to our questions about diseases that wildlife carry, almost all respondents were aware that there is a real and present risk of disease spillover from wildlife to people," the authors conclude. Further, they write, "Epidemics in recent years may contribute to this knowledge, but for hunters this awareness does not appear to influence or motivate any precautionary behaviors during the harvest of wildlife, as virtually no respondents reported taking precautions." In fact, financial gain was the hunters' primary motivation.In an unexpected twist, the survey results reveal that the majority of women who cook believe that hunters and dealers never or rarely disguise primate meat as another kind of meat in the marketing process. However, the majority of hunters report that they usually disguise primate meat as another kind of meat. The women overwhelmingly report they prefer to avoid purchasing primate meat. "Primates, rodents, and bats have long been investigated as important groups in zoonotic spillover events," says Dell. "While rodents and bats demonstrate high species diversity within their groups that contributes to their high microbial diversity, primates are closely related to humans and are believed to share many pathogens with humans, facilitating transmission. These findings raise concerns, as the ability of cooks to know and assess the risks of handing primate meat is subverted through the disguise of these species in the market."These data, and more outlined in the paper including perceptions of disease prevalence and transmission as well as hunting and marketing practices, help clarify where hunters and cooks are most susceptible to injury and exposure to infectious agents."Expanding our knowledge of awareness, perceptions and risks enables us to identify opportunities to mitigate infections and injury risk and promote safe handling practices," comments Dell. What's more, Souza says advancing the knowledge of community practices may assist public health officials as they work to help communities and individuals mitigate their own disease risk.Willcox adds that the data may ultimately lead to the development of more successful and appropriate conservation tactics for wildlife species in general and specifically in Uganda's Murchison Falls National Park. | Microbes | 2,020 |
October 19, 2020 | https://www.sciencedaily.com/releases/2020/10/201019155926.htm | Scientists find medieval plague outbreaks picked up speed over 300 years | McMaster University researchers who analyzed thousands of documents covering a 300-year span of plague outbreaks in London, England, have estimated that the disease spread four times faster in the 17th century than it had in the 14th century. | The findings, published today in the Researchers found that in the 14th century, the number of people infected during an outbreak doubled approximately every 43 days. By the 17th century, the number was doubling every 11 days."It is an astounding difference in how fast plague epidemics grew," says David Earn, a professor in the Department of Mathematics & Statistics at McMaster and investigator with the Michael G. DeGroote Institute for Infectious Disease Research, who is lead author on the study.Earn and a team including statisticians, biologists and evolutionary geneticists estimated death rates by analyzing historical, demographic and epidemiological data from three sources: personal wills and testaments, parish registers, and the London Bills of Mortality.It was not simply a matter of counting up the dead, since no published records of deaths are available for London prior to 1538. Instead, the researchers mined information from individual wills and testaments to establish how the plague was spreading through the population."At that time, people typically wrote wills because they were dying or they feared they might die imminently, so we hypothesized that the dates of wills would be a good proxy for the spread of fear, and of death itself. For the 17th century, when both wills and mortality were recorded, we compared what we can infer from each source, and we found the same growth rates," says Earn. "No one living in London in the 14th or 17th century could have imagined how these records might be used hundreds of years later to understand the spread of disease."While previous genetic studies have identified Yersinia pestis as the pathogen that causes plague, little is known about how the disease was transmitted."From genetic evidence, we have good reason to believe that the strains of bacterium responsible for plague changed very little over this time period, so this is a fascinating result," says Hendrik Poinar, a professor in the Department of Anthropology at McMaster, who is also affiliated with the Michael G. DeGroote Institute for Infectious Disease Research, and is a co-author on the study.The estimated speed of these epidemics, along with other information about the biology of plague, suggest that during these centuries the plague bacterium did not spread primarily through human-to-human contact, known as pneumonic transmission. Growth rates for both the early and late epidemics are more consistent with bubonic plague, which is transmitted by the bites of infected fleas.Researchers believe that population density, living conditions and cooler temperatures could potentially explain the acceleration, and that the transmission patterns of historical plague epidemics offer lessons for understanding COVID-19 and other modern pandemics.This new digitized archive developed by Earn's group provides a way to analyze epidemiological patterns from the past and has the potential to lead to new discoveries about how infectious diseases, and the factors that drive their spread, have changed through time. | Microbes | 2,020 |
October 19, 2020 | https://www.sciencedaily.com/releases/2020/10/201019145546.htm | CRISPR-induced immune diversification in host-virus populations | Just like humans, microbes have equipped themselves with tools to recognize and defend themselves against viral invaders. In a continual evolutionary battle between virus and host, CRISPR-Cas act as a major driving force of strain diversity in host-virus systems. | A new study led by Professor of Life Sciences Shai Pilosof (Ben-Gurion University of the Negev, Beer-Sheva, Israel), Professor of Microbiology Rachel Whitaker (University of Illinois Urbana-Champaign), and Professor of Ecology and Evolution Mercedes Pascual (University of Chicago) highlights the role of diversified immunity in mediating host-pathogen interactions and its eco-evolutionary dynamics. The study also included Professor of Bioengineering and Bliss Faculty Scholar Sergei Maslov (University of Illinois Urbana-Champaign), Sergio A. Alcal´a-Corona (University of Chicago), and PhD graduate students Ted Kim and Tong Wang (University of Illinois Urbana-Champaign).Their findings were reported in the journal "The motivation for this study was to figure out how the structure of immunity in microbial populations impacts the dynamics of virus-host interactions," said Whitaker.Now famous for its application in genetic engineering (Nobel Prize in Chemistry, 2020), the CRISPR-Cas system originated as an adaptive immune system for microbes. In this system, "protospacers" -- segments of DNA from the infecting virus -- are incorporated into the microbial host genome, termed "spacers." The host molecular machinery uses these spacers to recognize, target and destroy viruses, analogous to the human adaptive immune system.Researchers used computational models to explore the influence of microbial immune diversity on population dynamics of host-virus interactions. Their simulations revealed two alternating major regimes: the virus diversification regime (VDR) where viruses proliferate and diversify, and the host-controlled regime (HCR) where hosts constrain virus diversification, leading to their extinction.As the viruses diversified in VDR regimes, so too did the hosts. The viruses that were able to escape host control harbored mutations in their protospacers, thereby leading to higher encounter rates with hosts. From these increased encounters, hosts were able to acquire new spacers, increasing CRISPR diversity. In turn, the immunity network exhibited weighted-nestedness, which enabled host control."Weighted-nestedness means that some microbial strains have redundant immunity to many viruses while others have limited immunity to a few," said Whitaker. "It is this structure that leads to the dynamics of host stability punctuated by viral epidemics."To test the weighted-nestedness immunity structure predicted by their theory, researchers compared the data to empirical datasets from natural systems. Their findings revealed the presence of virus control via distributed and redundant immunity in these static empirical datasets."We next want to test this model in dynamic natural systems," said Whitaker. "We are focused on collecting high-resolution temporal data on hot springs and wastewater treatment because they are relatively simple with few viruses and microbial species."By understanding the dynamics of host-virus populations in natural systems, researchers can better control microbes in industrial settings."Some industrial applications like wastewater treatment, yogurt, and solvent production depend on stable microbial populations," said Whitaker. "Often, these applications fail because of viral epidemics that kill these microbes. We believe that understanding CRISPRs diversity and structure can support the design of stable microbial populations that are immune to virus infection."This work was funded by the Paul G. Allen Family Foundation through an Allen Distinguished Investigator award. | Microbes | 2,020 |
October 19, 2020 | https://www.sciencedaily.com/releases/2020/10/201019133654.htm | How some single-cell organisms control microbiomes | Large swaths of single-celled eukaryotes, non-bacterial single-cell organisms like microalgae, fungi or mold, can control microbiomes (a collection of tiny microbes, mostly bacteria) by secreting unusual small molecules around their cells, maintaining host survival and ecological success, according to a new study by NYU Abu Dhabi (NYUAD) Assistant Professor of Biology Shady Amin. | Research in the past decade has shown that most eukaryotes need microbiomes to survive. While we understand how large eukaryotes, like humans, corals and plants, control their microbiomes, scientists do not know how single-celled eukaryotes, like microalgae, do so.In humans, microbiomes can influence digestion, physical features, weight, susceptibility to disease, and even mental health. In corals, microbiomes sustain corals and enable them to withstand environmental change. In trees, microbiomes provide essential nutrients that enable forests and agricultural crops to grow. In microalgae, these microbiomes provide vitamins and other nutrients that keep microalgae alive.In the paper, The findings will enable scientists to predict how climate change will impact fisheries and atmospheric gas composition because single-celled eukaryotes in the oceans are responsible for a significant fraction of oxygen production on Earth and support the marine food web, including the fish and corals. The findings will also help expand scientists' understanding of evolution since single-celled eukaryotes constitute a significant fraction of life on earth."The discovery that a cryptic chemical language enables some single-celled eukaryotes to manipulate bacterial behavior is significant since most eukaryotes on Earth are single-celled and many are essential for our survival, " said Amin. | Microbes | 2,020 |
October 19, 2020 | https://www.sciencedaily.com/releases/2020/10/201019103453.htm | Natural killer cells also have a memory function | Good news for the human immune system: researchers from MedUni Vienna's Departments of Dermatology and Surgery have managed to ascribe an immunological memory function to a subset of cytotoxic NK cells, which have hitherto been regarded as antigen-non-specific. The researchers found under the leadership of Georg Stary, who is also Co-Director of the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases and affiliated with the CeMM (Research Center for Molecular Medicine of the Austrian Academy of Sciences) that around one third of all human liver NK cells can remember viruses and therefore respond specifically to them. These cells are therefore an interesting target for prophylactic use in the human immune system in the fight against infections and viruses. | NK cells are natural cytotoxic killer cells in human blood and are a type of lymphocyte, a subgroup of white blood cells or leukocytes. They are able to identify and kill abnormal cells such as tumour cells or virally infected cells (apoptosis). Up until now, NK cells have been regarded as having no memory function, meaning that they are unable to kill on an "antigen-specific" basis but are only able to react afresh each time to viruses and sources of infection in a non-specific way.In the study recently published in the top journal "Our study results show that this particular subset of NK cells mediates effective antigen-specific processes. This subset of NK cells could therefore be a suitable candidate for specific, therapeutic and also prophylactic vaccination strategies," summarises Stary. Healthy people have around 5 -- 15% of NK cells in their blood, whereby the liver acts as a reservoir for these cells. As a next step, the authors are investigating the role of these NK cells in the course of infectious diseases. They also want to explore whether these NK cells could additionally take over missing memory functions in patients with rare diseases with immunodeficiencies affecting T and B lymphocytes. | Microbes | 2,020 |
October 16, 2020 | https://www.sciencedaily.com/releases/2020/10/201016164320.htm | Those funky cheese smells allow microbes to 'talk' to and feed each other | Researchers at Tufts University have found that those distinctly funky smells from cheese are one way that fungi communicate with bacteria, and what they are saying has a lot to do with the delicious variety of flavors that cheese has to offer. The research team found that common bacteria essential to ripening cheese can sense and respond to compounds produced by fungi in the rind and released into the air, enhancing the growth of some species of bacteria over others. The composition of bacteria, yeast and fungi that make up the cheese microbiome is critical to flavor and quality of the cheese, so figuring out how that can be controlled or modified adds science to the art of cheese making. | The discovery, published in "Humans have appreciated the diverse aromas of cheeses for hundreds of years, but how these aromas impact the biology of the cheese microbiome had not been studied," said Benjamin Wolfe, professor of biology in the School of Arts and Science at Tufts University and corresponding author of the study. "Our latest findings show that cheese microbes can use these aromas to dramatically change their biology, and the findings' importance extends beyond cheese making to other fields as well."Many microbes produce airborne chemical compounds called volatile organic compounds, or VOCs, as they interact with their environment. A widely recognized microbial VOC is geosmin, which is emitted by soil microbes and can often be smelled after a heavy rain in forests. As bacteria and fungi grow on ripening cheeses, they secrete enzymes that break down amino acids to produce acids, alcohols, aldehydes, amines, and various sulfur compounds, while other enzymes break down fatty acids to produce esters, methyl ketones, and secondary alcohols. All of those biological products contribute to the flavor and aroma of cheese and they are the reason why Camembert, Blue cheese and Limburger have their signature smells.The Tufts researchers found that VOCs don't just contribute to the sensory experience of cheese, but also provide a way for fungi to communicate with and "feed" bacteria in the cheese microbiome. By pairing 16 different common cheese bacteria with 5 common cheese rind fungi, the researchers found that the fungi caused responses in the bacteria ranging from strong stimulation to strong inhibition. One bacteria species, Vibrio casei, responded by growing rapidly in the presence of VOCs emitted by all five of the fungi. Other bacteria, such as Psychrobacter, only grew in response to one of the fungi (Galactomyces), and two common cheese bacteria decreased significantly in number when exposed to VOCs produced by Galactomyces.The researchers found that the VOCs altered the expression of many genes in the bacteria, including genes that affect the way they metabolize nutrients. One metabolic mechanism that was enhanced, called the glyoxylate shunt, allows the bacteria to utilize more simple compounds as "food" when more complex sources such as glucose are unavailable. In effect, they enabled the bacteria to better "eat" some of the VOCs and use them as sources for energy and growth."The bacteria are able to actually eat what we perceive as smells," said Casey Cosetta, post-doctoral scholar in the department of biology at Tufts University and first author of the study. "That's important because the cheese itself provides little in the way of easily metabolized sugars such as glucose. With VOCs, the fungi are really providing a useful assist to the bacteria to help them thrive."There are direct implications of this research for cheese producers around the world. When you walk into a cheese cave there are many VOCs released into the air as the cheeses age. These VOCs may impact how neighboring cheeses develop by promoting or inhibiting the growth of specific microbes, or by changing how the bacteria produce other biological products that add to the flavor. A better understanding of this process could enable cheese producers to manipulate the VOC environment to improve the quality and variety of flavors.The implications of the research can even extend much further. "Now that we know that airborne chemicals can control the composition of microbiomes, we can start to think about how to control the composition of other microbiomes, for example in agriculture to improve soil quality and crop production and in medicine to help manage diseases affected by the hundreds of species of bacteria in the body," said Wolfe. | Microbes | 2,020 |
October 15, 2020 | https://www.sciencedaily.com/releases/2020/10/201015111733.htm | Inexpensive and rapid testing of drugs for resistant infections possible | A rapid and simple method for testing the efficacy of antibacterial drugs on infectious microbes has been developed and validated by a team of Penn State researchers. | Antimicrobial resistant infection is one of the major threats to human health globally, causing 2.5 million infections and 35,000 deaths annually, with the potential to grow to 10 million deaths annually by 2050 without improved techniques for detection and treatment.Several rapid testing techniques have been developed, but they do not live up to the reliability of the gold standard technology, which requires 18 to 24 hours for reliable results. In many cases, patients need to be treated with antibiotics in a crisis, leading clinicians to prescribe broad-spectrum antibiotics that may actually lead to greater drug resistance or unacceptable side effects."Compared to other methods of detection, our method does not require complex systems and measurement setups," says Aida Ebrahimi, assistant professor of electrical engineering and a senior author on a paper recently posted online in the journal The team tested their method against three strains of bacteria, including a resistant strain, to prove its effectiveness in the lab. Upon further development and validation with a broader range of pathogens and antibiotics, their method can allow physicians to prescribe the minimum dosage of the necessary drug, called the minimum inhibitory concentration (MIC) in a timely fashion.A phenomenon that other tests fail to account for is that bacteria may initially appear to be dead, but then can revive and multiply after many hours. The team's technology, augmented by machine learning, can predict whether the bacteria will revive or are actually dead, which is critical for accurate determination of the MIC value.Their technique is called dynamic laser speckle imaging."The main advantages of our method are the speed and simplicity," explained Zhiwen Liu, professor of electrical engineering and the second corresponding author. You shine a laser beam on the sample and get all of these light scattering speckles. We can then capture these images and subject them to machine learning analysis. We capture a series of images over time, which is the dynamic part. If the bacteria are alive, you are going to get some motion, such as a small vibration or a little movement. You can get reliable, predictive results quickly, for example within one hour."In addition to the immediate benefits provided to the patient, the lower concentration of drugs entering the water supply translates to less pollution to the environment, he says."One of the exciting aspects of this research has been its multidisciplinary nature. As an electrical engineer, I find it quite fascinating to work on designing and developing an optical diagnostic system as well as performing microbiology assays," said Keren Zhou, the co-lead first author on the paper and a doctoral student in electrical engineering.His co-lead author, doctoral student Chen Zhou, added, "We plan to further develop our technique to a low-cost and portable platform, which would be especially beneficial for resource-limited settings." | Microbes | 2,020 |
October 14, 2020 | https://www.sciencedaily.com/releases/2020/10/201014141032.htm | COVID-19 rapid test has successful lab results, research moves to next stages | Rapid detection of the SARS-CoV-2 virus, in about 30 seconds following the test, has had successful preliminary results in Mano Misra's lab at the University of Nevada, Reno. The test uses a nanotube-based electrochemical biosensor, a similar technology that Misra has used in the past for detecting tuberculosis and colorectal cancer as well as detection of biomarkers for food safety. | Professor Misra, in the University's College of Engineering Chemical and Materials Department, has been working on nano-sensors for 10 years. He has expertise in detecting a specific biomarker in tuberculosis patients' breath using a metal functionalized nano sensor."I thought that similar technology can be used to detect the SARS-CoV-2 virus, which is a folded protein," Misra said. "This is Point of Care testing to assess the exposure to COVID-19. We do not need a laboratory setting or trained health care workers to administer the test. Electrochemical biosensors are advantageous for sensing purposes as they are sensitive, accurate and simple."The test does not require a blood sample, it is run using a nasal swab or even exhaled breath, which has biomarkers of COVID-19. Misra and his team have successfully demonstrated a simple, inexpensive, rapid and non-invasive diagnostic platform that has the potential to effectively detect the SARS-CoV-2 virus.The team includes Associate Professor Subhash Verma, virologist, and Research Scientist Timsy Uppal at the University's School of Medicine, and Misra's post-doctoral researcher Bhaskar Vadlamani."Our role on this project is to provide viral material to be used for detection by the nanomaterial sensor developed by Mano," Verma said. "Mano contacted me back in April or May and asked whether we can collaborate to develop a test to detect SARS-CoV-2 infection by analyzing patients' breath. That's where we came in, to provide biological material and started with providing the surface protein of the virus, which can be used for detecting the presence of the virus."Verma, an expert on SARS-CoV-2, synthesized and prepared the antigenic protein of COVID-19 virus in his laboratory, SARS-CoV-2 receptor binding domain protein, for the preliminary testing and determining the sensitivity of our nano sensor. Synthesizing and purification of viral proteins is usual and routine work in a virology laboratory."Our lab is a virology laboratory, which works on different viruses, and we have been working on SARS-CoV-2 from the beginning of the outbreak," he said. "Our genomics and diagnostic group have been sequencing the SARS-CoV-2 from the nasal swabs of COVID-19 patients of the state of Nevada to determine mutational changes in the virus while SARS-CoV-2 circulates in our population."The team developed co-metal functionalized nanotubes as a sensing material for electrochemical detection of the protein. They confirmed the biosensor's potential for clinical application by directly analyzing the RBD of the Spike glycoprotein on the sensor.The team plans to move to the next step of sensor validation on the actual COVID-19 patients swabs stored in the Viral Transport Medium and have applied for funding to develop a specific and inexpensive point-of-care sensor for a rapid detection of COVID-19 virus in saliva or breath of infected individuals.The developed approach also has the potential for diagnosis of other respiratory viral diseases by identifying appropriate metallic elements to functionalize nanotubes.The team's article "Functionalized TiO2 nanotube-based Electrochemical Biosensor for Rapid Detection of SARS-CoV-2" has been accepted for publication in the biosensors section of the MDPI publication ' | Microbes | 2,020 |
October 14, 2020 | https://www.sciencedaily.com/releases/2020/10/201014114652.htm | World first study shows that some microorganisms can bend the rules of evolution | In a world first Monash University scientists have discovered that HGT can bend the rules of evolution. | The discovery is outlined in a study published today in "HGT is very important in microbial evolution, especially for the evolution of antibiotic resistance in human pathogens," said Dr McDonald."Genes for antibiotic resistance in the bacteria that live in hospitals, sewers and farms, are common because there are antibiotics in these places, due to human activities," he said."However, when scientists check environments without antibiotics, for example, forests or estuaries, antibiotic resistance genes can still be detected."Dr McDonald and his team of researchers conducted an evolution experiment to study how the genes that cause antibiotic resistance spread in the environment.They tested antibiotic-sensitive bacteria in growth media without antibiotics. But they allowed this bacteria to receive HGT from other antibiotic-resistant bacteria."We used whole genome sequencing to confirm whether the genes for antibiotic resistance were spreading in the populations, even without selection," Dr McDonald said."Later we challenged our evolved populations with high concentrations of antibiotic."We found that the populations that had received HGT could survive treatment by antibiotic, but the control populations that had not received HGT did not survive."The researchers found that antibiotic resistance genes can spread into populations that are not experiencing selection with antibiotic, and that, even though these genes were at low levels, they prepared the population for future challenges with antibiotic."This could explain why antibiotic resistance evolves so quickly in hospitals," Dr McDonald said."Our study shows for the first time how antibiotic resistance genes can stay in a population, even when there is not antibiotic selection pressure," he said."This could also explain why patients still have antibiotic resistant bacteria long after they have finished treatment with antibiotic and why bacteria quickly evolve resistance even when they have not been exposed to antibiotic before."Dr McDonald said the study was important because showed how HGT can bend the rules of evolution.It was previously thought that the only genes that could spread through a population were those that caused a benefit 'right now' (in the environment that the population is experiencing at that point in time).This is because natural selection should push low fitness, deleterious genes out of the population."But our work shows that if HGT can transfer enough of the gene into the population, it can provide a force that pushes back against natural selection, and allows genes that do not confer a benefit to spread in the population," Dr McDonald said. | Microbes | 2,020 |
October 13, 2020 | https://www.sciencedaily.com/releases/2020/10/201013124050.htm | Computer model uses virus 'appearance' to better predict winter flu strains | Combining genetic and experimental data into models about the influenza virus can help predict more accurately which strains will be most common during the next winter, says a study published recently in | The models could make the design of flu vaccines more accurate, providing fuller protection against a virus that causes around half a million deaths each year globally.Vaccines are the best protection we have against the flu. But the virus changes its appearance to our immune system every year, requiring researchers to update the vaccine to match. Since a new vaccine takes almost a year to make, flu researchers must predict which flu viruses look the most like the viruses of the future.The gold-standard ways of studying influenza involve laboratory experiments looking at a key molecule that coats the virus called haemagglutinin. But these methods are labour-intensive and take a long time. Researchers have focused instead on using computers to predict how the flu virus will evolve from the genetic sequence of haemagglutinin alone, but these data only give part of the picture."The influenza research community has long recognised the importance of taking into account physical characteristics of the flu virus, such as how haemagglutinin changes over time, as well as genetic information," explains lead author John Huddleston, a PhD student in the Bedford Lab at Fred Hutchinson Cancer Research Center and Molecular and Cell Biology Program at the University of Washington, Seattle, US. "We wanted to see whether combining genetic sequence-only models of influenza evolution with other high-quality experimental measurements could improve the forecasting of the new strains of flu that will emerge one year down the line."Huddleston and the team looked at different components of virus 'fitness' -- that is, how likely the virus is to thrive and continue to evolve. These included how similar the antigens of the virus are to previously circulating strains (antigens being the components of the virus that trigger an immune response). They also measured how many mutations the virus has accumulated, and whether they are beneficial or harmful.Using 25 years of historical flu data, the team made forecasts one year into the future from all available flu seasons. Each forecast predicted what the future virus population would look like using the virus' genetic code, the experimental data, or both. They compared the predicted and real future populations of flu to find out which data types were more helpful for predicting the virus' evolution.They found that the forecasts that combined experimental measures of the virus' appearance with changes in its genetic code were more accurate than forecasts that used the genetic code alone. Models were most informative if they included experimental data on how flu antigens changed over time, the presence of likely harmful mutations, and how rapidly the flu population had grown in the past six months. "Genetic sequence alone could not accurately predict future flu strains -- and therefore should not take the place of traditional experiments that measure the virus' appearance," Huddleston says."Our results highlight the importance of experimental measurements to quantify the effects of changes to virus' genetic code and provide a foundation for attempts to forecast evolutionary systems," concludes senior author Trevor Bedford, Principal Investigator at the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. "We hope the open-source forecasting tools we have developed can immediately provide better forecasts of flu populations, leading to improved vaccines and ultimately fewer illnesses and deaths from flu." | Microbes | 2,020 |
October 12, 2020 | https://www.sciencedaily.com/releases/2020/10/201008121306.htm | Mechanical forces of biofilms could play role in infections | Studying bacterial biofilms, EPFL scientists have discovered that mechanical forces within them are sufficient to deform the soft material they grow on, e.g. biological tissues, suggesting a "mechanical" mode of bacterial infection. | The vast majority of bacteria in the world live on surfaces by forming structures called "biofilms." These communities host thousands to millions of bacteria of different types, and are so biologically complex and active that scientists describe them as "cities."Biofilms are in fact the preferred lifestyle of bacteria. They form them by attaching to each other on surfaces as diverse as the ocean floor, internal organs and teeth: dental plaque is a common example of a biofilm. But biofilms also cause chronic infections, e.g. the opportunistic pathogen Generally speaking, the interaction between biofilm and host is thought to be biochemical. But there is some evidence to suggest that the physical, mechanical interplay between them might be just as important -- and overlooked as an influence on the host's physiology. For example, how do biofilms form on soft, tissue-like materials?This is the question that a team of scientists led by Alex Persat at EPFL have ventured to answer. Publishing in the journal When bacteria form biofilms, they attach onto a surface and begin to divide. At the same time, they bury themselves inside a mix of polysaccharides, proteins, nucleic acids, and debris from dead cells. This mix forms a sticky substance that is called the "EPS" matrix (EPS stands for "extracellular polymeric substances").As single bacteria grow inside the EPS they stretch or compress it, exerting mechanical stress. The growth of the biofilm and the EPS matrix's elastic properties generate internal mechanical stress.The scientists grew biofilms on soft hydrogel surfaces and measured how they exerted forces upon variations of EPS components. This revealed that biofilms induce deformations by "buckling" like a carpet or a ruler. How big the deformations are depends on how stiff the "host" material is and on the composition of the EPS.The researchers also found that Professor Alexandre Persat's' lab is part of EPFL's Global Health Institute, situated in the School of Life Sciences. | Microbes | 2,020 |
October 8, 2020 | https://www.sciencedaily.com/releases/2020/10/201008104232.htm | Bacterial cellulose degradation system could give boost to biofuels production | Researchers have uncovered details of how a certain type of bacteria breaks down cellulose -- a finding that could help reduce the cost and environmental impact of the use of biomass, including biofuel production. The bacteria's cellulose degradation system is in some way different from how a fungus is already widely used in industry, including to soften up denim to make stone-washed jeans. | Efforts to find ways to break down cellulose, the tough stuff that makes up plant cell walls, faster and more productively has long been a goal of industrial researchers.When plants are processed into biofuels or other biomass applications, cellulose has to be degraded into simpler sugar molecules first, and this step can represent up to a quarter of the operating and capital costs of biofuel production. If this process can be made faster and more productive, it won't just save industry money, but such efficiencies could also reduce the environmental impact of production.Cellulose molecules bind very strongly to each other, making cellulose very hard to break down. Some fungi are able to break it down, however, and their cellulose degradation systems are well known.Fungi produce many types of But there is another type of cellulose degradation system used by some bacteria, and which is similar in many ways to that used by this fungus. But this system has not been very well understood until now. In a paper in the The type of cellobiohydrolase produced by the bacterium But the two systems have different carbohydrate-binding modules (the series of proteins in the enzyme that bind to the carbohydrates in the cellulose) and what are termed "linkers," in essence the part of the enzyme that links the catalytic domain to the carbohydrate-binding modules.In earlier research, the NINS scientists had already established that the structure of the linker region of the fungal cellobiohydrolase played a crucial role in how fast the enzyme binds to cellulose (and thus how fast the system degrades cellulose)."So the obvious next questions were: Even though these other parts of the bacterium's cellobiohydrolase are different to those of the fungus, do they nevertheless do something similar?" said Akihiko Nakamura and Ryota Iino, the researchers on the team. "Do they also speed up cellulose degradation?"They found that they do. The scientists used single-molecule fluorescence imaging -- an advanced method of microscopy that delivers images of living cells with a resolution of just tens of nanometers -- to observe the bacterium's cellobiohydrolase binding to and dissociating from cellulose molecules.This allowed them to clarify the functions of the different parts of the cellulose degradation system. They found that the carbohydrate-binding modules were indeed important for the initial binding, but the role played by the linker region was fairly minor.However, they found that the catalytic domain was not so similar after all. Its structure showed longer loops at the entrance and exit of a "tunnel" in the heart of the system compared to that of the fungus. And this difference in the tunnel structure results in higher processivity -- the ability of an enzyme to set off multiple consecutive reactions.The next steps will be to engineer these bacterial cellulose degrading enzymes to break down cellulose faster. | Microbes | 2,020 |
October 8, 2020 | https://www.sciencedaily.com/releases/2020/10/201007182334.htm | Detecting SARS-CoV-2 in the environment | Researchers have outlined an approach to characterize and develop an effective environmental monitoring methodology for SARS CoV-2 virus, that can be used to better understand viral persistence in built environments. The investigators from 7 institutions published their research this week in | "As we all know, SARS CoV-2 is of worldwide concern," said principal investigator of the study Dr. Kasthuri Venkateswaran, senior research scientist at NASA's Jet Propulsion Laboratory (JPL) in Southern California.For the studies, the researchers used inactivated noninfectious virus that is viable and can be used as a surrogate. "Our group adapted the CDC-approved reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) methodology and then tested the efficacy of RT-qPCR in detecting SARS CoV-2 from various environmental surface samples," said Dr. Ceth W. Parker, one of the 3 lead study authors, a post-doctoral fellow at JPL. The researchers tested a variety of surface materials common in built environments, including bare stainless steal, painted stainless steel, plastics and reinforced fiberglass."We tested these surfaces by seeding inactivated noninfectious SARS CoV-2 particles and then determining how well we could actually recover them from the surfaces," said Dr. Parker. "It takes a minimum of 1,000 viral particles per 25 cm2 to effectively and reproducibly detect SARS-CoV-2 virus on the surface. We found that viral RNA can persist on surfaces for at least 8 days. We also found that inhibitory substances and debris have to be taken into account on the surfaces they are being tested on." | Microbes | 2,020 |
October 7, 2020 | https://www.sciencedaily.com/releases/2020/10/201002091031.htm | Vaccine ingredients could be hiding in small molecule libraries | Many vaccines include ingredients called adjuvants that help make them more effective by eliciting a stronger immune response. Identifying potential adjuvants just got easier, thanks to an approach described by scientists at Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS) and colleagues in the journal | The team of chemists and biologists in Japan report they found a molecule that, when added to a vaccine, strengthens the immune response just as well as a commonly used adjuvant. Vaccine adjuvants are an essential part of clinically used antigen vaccines, such as influenza, hepatitis and cervical cancer vaccines."Adjuvants generate a robust and long-lasting immune response, but the ones currently in use, like aluminium salts and oil-in-water emulsions, were developed in the 1920s and we don't precisely understand how they work, which is why they are often called 'immunologists' dirty little secret,'" says iCeMS chemical biologist Motonari Uesugi, who led the study.The new adjuvant was discovered by screening a library of 8,000 small molecules for their ability to self-assemble. Molecular self-assembly is the spontaneous self-organization of molecules through non-electron-sharing bonds. This is a well-known concept in materials science that is also employed by living organisms to perform complex biological functions."We hypothesized that structures that come together through molecular self-assembly might mimic structures in pathogens, like viruses, stimulating a similar immune response," says Uesugi.The team found 116 molecules that can self-assemble and then screened them for the ability to increase interleukin-6 expression by macrophages. Macrophages are immune cells that detect and 'eat up' pathogens circulating in the body. They also release proteins, such as interleukin-6, that activate other immune cells.The research led to the discovery of a molecule called cholicamide. This molecule self-assembled to form a virus-mimicking structure that is engulfed by macrophages and similar immune cells. The structures are transported into specialized vacuoles to combine with a specific receptor called toll-like receptor 7, which sparks a heightened immune response. Specifically, it leads to the release of immune-stimulating cues like interleukin-6.Further investigations and comparisons demonstrated that cholicamide was just as potent in inducing an immune response as the adjuvant Alum when added to an influenza vaccine given to mice."Our study, to the best of our knowledge, is the first report of using a small molecule library for vaccine adjuvant discovery," says Uesugi. "We hope the new approach paves the way for discovering and designing self-assembling small molecule adjuvants against pathogens, including emerging viruses."Further studies are needed to determine how cholicamide mimics the single RNA strands of viruses to activate toll-like receptor 7. The researchers also want to understand how cholicamide binds to the receptor to elucidate the effects of this interaction. | Microbes | 2,020 |
October 6, 2020 | https://www.sciencedaily.com/releases/2020/10/201006132122.htm | There's a reason bacteria stay in shape | Fat bacteria? Skinny bacteria? From our perspective on high, they all seem to be about the same size. In fact, they are. | Precisely why has been an open question, according to Rice University chemist Anatoly Kolomeisky, who now has a theory.A primal mechanism in bacteria that keeps them in their personal Goldilocks zones -- that is, just right -- appears to depend on two random means of regulation, growth and division, that cancel each other out. The same mechanism may give researchers a new perspective on disease, including cancer.The "minimal model" by Kolomeisky, Rice postdoctoral researcher and lead author Hamid Teimouri and Rupsha Mukherjee, a former research assistant at Rice now at the Indian Institute of Technology Gandhinagar, appears in the American Chemical Society's "Everywhere we see bacteria, they more or less have the same sizes and shapes," Kolomeisky said. "It's the same for the cells in our tissues. This is a signature of homeostasis, where a system tries to have physiological parameters that are almost the same, like body temperature or our blood pressure or the sugar level in our blood."Nature likes to have these parameters in a very narrow range so that living systems can work the most efficiently," he said. "Deviations from these parameters are a signature of disease."Bacteria are models of homeostasis, sticking to a narrow distribution of sizes and shape. "But the explanations we have so far are not good," Kolomeisky said. "As we know, science does not like magic. But something like magic -- thresholds -- is proposed to explain it."For bacteria, he said, there is no threshold. "Essentially, there's no need for one," he said. "There are a lot of underlying biochemical processes, but they can be roughly divided into two stochastic chemical processes: growth and division. Both are random, so our problem was to explain why these random phenomenon lead to a very deterministic outcome."The Rice lab specializes in theoretical modeling that explains biological phenomena including genome editing, antibiotic resistance and cancer proliferation. Teimouri said the highly efficient chemical coupling between growth and division in bacteria was far easier to model."We assumed that, at typical proliferation conditions, the number of division and growth protein precursors are always proportional to the cell size," he said. The model predicts when bacteria will divide, allowing them to optimize their function. The researchers said it agrees nicely with experimental observations and noted manipulating the formula to knock bacteria out of homeostasis proved their point. Increasing the theoretical length of post-division bacteria, they said, simply leads to faster rates of division, keeping their sizes in check."For short lengths, growth dominates, again keeping the bacteria to the right size," Kolomeisky said.The same theory doesn't necessarily apply to larger organisms, he said. "We know that in humans, there are many other biochemical pathways that might regulate homeostasis, so the problem is more complex."However, the work may give researchers new perspective on the proliferation of diseased cells and the mechanism that forces, for instance, cancer cells to take on different shapes and sizes."One of the ways to determine cancer is to see a deviation from the norm," Kolomeisky said. "Is there a mutation that leads to faster growth or faster division of cells? This mechanism that helps maintain the sizes and shapes of bacteria may help us understand what's happening there as well." | Microbes | 2,020 |
October 6, 2020 | https://www.sciencedaily.com/releases/2020/10/201006091226.htm | Supercharged 'clones' spark scarlet fever's re-emergence | A University of Queensland-led team of international researchers says supercharged "clones" of the bacteria | UQ's Dr Stephan Brouwer said health authorities globally were surprised when an epidemic was detected in Asian countries in 2011."The disease had mostly dissipated by the 1940s," Dr Brouwer said."Like the virus that causes COVID-19, "Scarlet fever commonly affects children, typically aged between two and 10 years."After 2011, the global reach of the pandemic became evident with reports of a second outbreak in the UK, beginning in 2014, and we've now discovered outbreak isolates here in Australia."This global re-emergence of scarlet fever has caused a more than five-fold increase in disease rate and more than 600,000 cases around the world."Co-author Professor Mark Walker and the team found a variety of "The toxins would have been transferred into the bacterium when it was infected by viruses that carried the toxin genes," Professor Walker said."We've shown that these acquired toxins allow "These supercharged bacterial clones have been causing our modern scarlet fever outbreaks."The research team then removed the toxin genes from the clones causing scarlet fever, and these modified 'knock-out' clones were found to be less able to colonise in an animal model of infection."For the time being, scarlet fever outbreaks have been dampened, largely due to public health policy measures introduced to control COVID-19."This year COVID-19 social distancing has kept scarlet fever outbreaks in check for now," Professor Walker said."And the disease's main target -- children -- have been at school less and also spending far less time in other large groups."But when social distancing eventually is relaxed, scarlet fever is likely to come back."We need to continue this research to improve diagnosis and to better manage these epidemics."Just like COVID-19, ultimately a vaccine will be critical for eradicating scarlet fever -- one of history's most pervasive and deadly childhood diseases." | Microbes | 2,020 |
October 5, 2020 | https://www.sciencedaily.com/releases/2020/10/201005101536.htm | Diagnosing COVID-19 in just 30 minutes | The year 2020 can be summarized simply by one word -- COVID-19 -- as it was the culprit that froze the entire world. For more than 8 months so far, movement between nations has been paralyzed all because there are no means to prevent or treat the virus and the diagnosis takes long. | In Korea, there are many confirmed cases among those arriving from abroad but diagnosis does not take place at the airport currently. Overseas visitors can enter the country if they show no symptoms and must visit the screening clinic nearest to their site of self-isolation on their own. Even this, when the clinic closes, they have no choice but to visit it the next day. Naturally, there have been concerns of them leaving the isolation facilities. What if there was a way to diagnose and identify the infected patients right at the airport?A joint research team comprising Professor Jeong Wook Lee and Ph.D. candidate Chang Ha Woo and Professor Gyoo Yeol Jung and Dr. Sungho Jang of the Department of Chemical Engineering at POSTECH have together developed a SENSR (SENsitive Splint-based one-pot isothermal RNA detection) technology that allows anyone to easily and quickly diagnose COVID-19 based on the RNA sequence of the virus.This technology can diagnose infections in just 30 minutes, reducing the stress on one single testing location and avoiding contact with infected patients as much as possible. The biggest benefit is that a diagnostic kit can be developed within week even if a new infectious disease appears other than COVID-19.The PCR molecular test currently used for COVID-19 diagnosis has very high accuracy but entails a complex preparation process to extract or refine the virus. It is not suitable for use in small farming or fishing villages, or airport or drive-thru screening clinics as it requires expensive equipment as well as skilled experts.RNA is a nucleic acid that mediates genetic information or is involved in controlling the expression of genes. The POSTECH researchers designed the test kit to produce nucleic acid binding reaction to show fluorescence only when COVID-19 RNA is present. Therefore, the virus can be detected immediately without any preparation process with high sensitivity in a short time. And it is as accurate as the current PCR diagnostic method.Using this technology, the research team found the SARS-CoV-2 virus RNA, the cause of COVID-19, from an actual patient sample in about 30 minutes. In addition, five pathogenic viruses and bacterial RNAs were detected which proved the kit's usability in detecting pathogens other than COVID-19.Another great advantage of the SENSR technology is the ease of creating the diagnostic device that can be developed into a simple portable and easy-to-use form.If this method is introduced, it not only allows onsite diagnosis before going to the screening clinic or being hospitalized, but also allows for a more proactive response to COVID-19 by supplementing the current centralized diagnostic system."This method is a fast and simple diagnostic technology which can accurately analyze the RNA without having to treat a patient's sample," commented Professor Jeong Wook Lee. "We can better prepare for future epidemics as we can design and produce a diagnostic kit for new infectious diseases within a week."Professor Gyoo Yeol Jung added, "The fact that pathogenic RNAs can be detected with high accuracy and sensitivity, and that it can be diagnosed on the spot is drawing attention from academia as well as industry circles." He explained, "We hope to contribute to our response to COVID-19 by enhancing the current testing system.The study, which was published in | Microbes | 2,020 |
October 2, 2020 | https://www.sciencedaily.com/releases/2020/10/201002153615.htm | New COVID test doesn't use scarce reagents, catches all but the least infectious | A major roadblock to large scale testing for coronavirus infection in the developing world is a shortage of key chemicals, or reagents, needed for the test, specifically the ones used to extract the virus's genetic material, or RNA. | A team of scientists at the University of Vermont, working in partnership with a group at the University of Washington, has developed a method of testing for the COVID-19 virus that doesn't make use of these chemicals but still delivers an accurate result, paving the way for inexpensive, widely available testing in both developing countries and industrialized nations like the United States, where reagent supplies are again in short supply.The method for the test, published Oct. 2 in The accuracy of the new test was evaluated by a team of researchers at the University of Washington led by Keith Jerome, director of the university's Molecular Virology Lab, using 215 COVID-19 samples that RT-PCR tests had shown were positive, with a range of viral loads, and 30 that were negative.It correctly identified 92% of the positive samples and 100% of the negatives.The positive samples the new test failed to catch had very low levels of the virus. Public health experts increasingly believe that ultra-sensitive tests that identify individuals with even the smallest viral loads are not needed to slow spread of the disease."It was a very positive result," said Jason Botten, an expert on pathogenic RNA viruses at the University of Vermont's Larner College of Medicine and senior author on the "You can go for the perfect test, or you can use the one that's going to pick up the great majority of people and stop transmission," Botten said. "If the game now is focused on trying to find people who are infectious, there's no reason why this test shouldn't be front and center, especially in developing countries where there are often limited testing programs because of reagent and other supply shortages."The standard PCR test has three steps, while this simpler version of the standard test has only two, Botten said."In step 1 of the RT-PCR test, you take the swab with the nasal sample, clip the end and place it in a vial of liquid, or medium. Any virus on the swab will transfer from the swab into the medium," he said. "In step 2, you take a small sample of the virus-containing medium and use chemical reagents, the ones that are often in short supply, to extract the viral RNA. In step 3, you use other chemicals to greatly amplify any viral genetic material that might be there. If virus was present, you'll get a positive signal."The new test skips the second step."It takes a sample of the medium that held the nasal swab and goes directly to the third, amplification step," Botten said, removing the need for scarce RNA extraction reagents as well as significantly reducing the time, labor and costs required to extract viral RNA from the medium in step 2.Botten said the test is ideally suited to screening programs, in both developed and developing countries, since it is inexpensive, takes much less processing time and reliably identifies those who are likely to spread the disease.Its low cost and efficiency could extend testing capacity to groups not currently being tested, Botten said, including the asymptomatic, nursing home residents, essential workers and school children. The standard RT-PCR test could be reserved for groups, like health care workers, where close to 100% accuracy is essential.The two-step test developed by the University of Vermont team first caught the attention of the scientific community in March, when preliminary results that accurately identified six positive and three negative Vermont samples were published as a preprint in bioRxiv, an open access repository for the biological sciences. The preprint was downloaded 18,000 times -- in its first week, it ranked 17th among 15 million papers the site had published -- and the abstract was viewed 40,000 times.Botten heard from labs around the world who had seen the preprint and wanted to learn more about the new test."They said, 'I'm from Nigeria or the West Indies. We can't test, and people's lives are at stake. Can you help us?'"Botten also heard from Syril Pettit, the director of HESI, the Health and Environmental Sciences Institute, a non-profit that marshals scientific expertise and methods to address a range of global health challenges, who had also seen the preprint.Pettit asked Botten to join a think tank of likeminded scientists she was organizing whose goal was to increase global testing capacity for COVID-19. The test developed by the University of Vermont and University of Washington teams would serve as a centerpiece. To catalyze a global response, the group published a call to action in And it took action, reaching out to 10 laboratories in seven countries, including Brazil, Chile, Malawi, Nigeria and Trinidad/Tobago, as well as the U.S. and France, to see if they would be interested in giving the two-step test a trial run. "Universally, the response was yes," Pettit said.The outreach led to a new HESI program called PROPAGATE. Each of the labs in the PROPAGATE Network will use the two-step test on a series of positive and negative samples sent to them by the University of Washington to see if they can replicate the results the university achieved.The study has already shown promising results. One of the labs in Chile has also used the test on its own samples from the community and got accurate results.Assuming all goes well, Pettit and her colleagues at the University of Vermont and the University of Washington as well as scientists from the 10 partner sites plan to publish the results."The goal is the make the two-step test accessible to any lab in the world facing these hurdles and see a broad uptake," she said. | Microbes | 2,020 |
October 1, 2020 | https://www.sciencedaily.com/releases/2020/10/201001113602.htm | Carb-eating bacteria under viral threat | Strictly speaking, humans cannot digest complex carbohydrates -- that's the job of bacteria in our large intestines. UC Riverside scientists have just discovered a new group of viruses that attack these bacteria. | The viruses, and the way they evade counterattack by their bacterial hosts, are described in a new Bacterioides can constitute up to 60% of all the bacteria living in a human's large intestine, and they're an important way that people get energy. Without them, we'd have a hard time digesting bread, beans, vegetables, or other favorite foods. Given their significance, it is surprising that scientists know so little about viruses that prey on Bacteroides."This is largely unexplored territory," said microbiologist Patrick Degnan, an assistant professor of microbiology and plant pathology, who led the research.To find a virus that attacks Bacteroides, Degnan and his team analyzed a collection of bacterial genomes, where viruses can hide for numerous generations until something triggers them to replicate, attack and leave their host. This viral lifestyle is not without risk as over time mutations could occur that prevent the virus from escaping its host.On analyzing the genome of Bacteroides vulgatus, Degnan's team found DNA belonging to a virus they named BV01. However, determining whether the virus is capable of escaping, or re-infecting its host, proved challenging."We tried every trick we could think of. Nothing in the laboratory worked until we worked with a germ-free mouse model," Degnan said. "Then, the virus jumped."This was possible due to Degnan's collaboration with UCR colleague, co-author and fellow microbiologist Ansel Hsiao.This result suggests conditions in mammalian guts act as a trigger for BV01 activity. The finding underscores the importance of both in vitro and in vivo experiments for understanding the biology of microbes.Looking for more information about the indirect effect of this bacterial virus might have on humans, Degnan's team determined that when BV01 infects a host cell, it disrupts how that cell normally behaves."Over 100 genes change how they get expressed after infection," Degnan said.Two of the altered genes that stood out to the researchers are both responsible for deactivating bile acids, which are toxic to microbes. The authors speculate that while this possibly alters the sensitivity of the bacteria to bile acids, it also may influence the ability of the bacteria to be infected by other viruses."This virus can go in and change the metabolism of these bacteria in human guts that are so key for our own metabolism," Degnan said.Though the full extent of BV01 infection is not yet known, scientists believe viruses that change the abundance and activity of gut bacteria contribute to human health and disease. One area for future studies will involve the effect of diet on BV01 and viruses like it, as certain foods can cause our bodies to release more bile.Degnan also notes that BV01 is only one of a group of viruses his team identified that function in similar ways. The group, Salyersviridae, is named after famed microbiologist Abigail Salyers whose work on intestinal bacteria furthered the science of antibiotic resistance.Further research is planned to understand the biology of these viruses."It's been sitting in plain sight, but no one has characterized this important group of viruses that affect what's in our guts until now," Degnan said. | Microbes | 2,020 |
October 1, 2020 | https://www.sciencedaily.com/releases/2020/10/201001113528.htm | Cause of 1990s Argentina cholera epidemic uncovered | The evolution of epidemic and endemic strains of the cholera-causing bacterium | The data have influenced health policy in Argentina, where the national alert surveillance system now uses whole-genome sequencing to distinguish between pandemic and non-pandemic lineages of Cholera, caused by strains of In a new study, the team sequenced the genomes of a unique set of historical Using phylogenetic analysis, they confirmed that the 1992 outbreak of cholera in Argentina was caused by one introduction of 7PET Matthew Dorman, first author on the study from the Wellcome Sanger Institute said: "When a 7PET pandemic strain enters into Latin America from elsewhere, it can cause massive epidemics, such as those seen in Peru in the 1990s and Haiti in 2010. If we are to control cholera epidemics efficiently, it is vital that we are able to distinguish and understand the differences between the local, endemic The findings have been used by public health authorities in Argentina, where the national alert system has now been changed to distinguish between pandemic 7PET lineage and local Dr Josefina Campos, senior author from INEI-ANLIS "Dr. Carlos G. Malbrán," Buenos Aires, Argentina said: "Thanks to a comprehensive surveillance and reporting system, the reference laboratory in Argentina contains a snapshot of an entire epidemic. This gave us a unique opportunity to understand the detailed evolution of Professor Nick Thomson, senior author from the Wellcome Sanger Institute and the London School of Hygiene and Tropical Medicine said: "Detailed studies like this contribute to our growing understanding of how cholera is moving across the globe: evidence to inform improved control strategies as well as identify areas for further research. Our challenge is to better understand why such a simple bacterium continues to pose such a threat to human health, with this study we are a little step closer." | Microbes | 2,020 |
October 1, 2020 | https://www.sciencedaily.com/releases/2020/10/201001113648.htm | Cells sacrifice themselves to boost immune response to viruses | Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection. New research appearing in the journal | "The immune system consists of several different types of cells, all acting in coordination," said Minsoo Kim, Ph.D., a professor of Microbiology and Immunology at the University of Rochester Medical Center (URMC) and senior author of the study. "These findings show that cells called neutrophils play an important altruistic role that benefits other immune cells by providing key resources for their survival and, in the process, enhancing the body's immune response against a virus."Neutrophils are a key component of the innate immune system, the part of the body's defenses that is always switched on and alert for bacterial and viral invaders. The vast majority of white cells circulating in blood are neutrophils and, as a result, these cells are the first on the scene to respond to an infection.However, neutrophils are not fully equipped to eliminate a viral threat by themselves. Instead, when the respiratory tract is infected with a virus like influenza or COVID-19, a large number of neutrophils rush to the infection site and release chemical signals. This triggers the production of specialized T cells, which are part of the body's adaptive immune system, which is activated to produce a more direct response to specific infections. Once mobilized in sufficient quantities, a process that typically takes several days, these T cells target and ultimately destroy the infected cells.The new study, which was conducted in mice infected with the flu virus, shows that in addition to jump-starting the adaptive immune response, neutrophils have one more important mission that requires that they sacrifice themselves. As T cells arrive at the infection site, the neutrophils initiate a process called apoptosis, or controlled death, which releases large quantities of a molecule called epidermal growth factor (EGF). EGF provides T cells with the extra boost in energy necessary to finish the job."This study represents an important paradigm shift and shows that the adaptive immune system doesn't generate a successful response without instruction and help from the innate immune system," said Kim. "The findings reveal, for the first time, how different immune cells work together, and even sacrifice themselves, to accomplish the same goal of protecting the host from the viral infection."Kim and his colleagues point out that this new understanding of how the immune system functions opens the door to potential new methods to intervene and optimize the collaboration between different immune cells during viral infection. These efforts could ultimately lead to more effective vaccines and anti-viral therapies for respiratory infections like the flu and coronavirus. | Microbes | 2,020 |
October 1, 2020 | https://www.sciencedaily.com/releases/2020/10/201001090138.htm | Medical mystery: 'Creeping fat' in Crohn's patients linked to bacteria | In many patients with Crohn's disease abdominal fat migrates to the wall of the inflamed small intestines. What prompts the fat tissue to "creep" through the abdomen and wrap around the intestines of many patients with this inflammatory bowel disease (IBD) has been an enduring mystery. | Now, investigators have identified a critical clue. In a study published in the journal CELL this week, researchers from Cedars-Sinai show that the peculiar creeping activity of the fat appears to initially be protective but then ends up doing more harm than good."Creeping fat is often a landmark for surgeons performing resections on an IBD patient's bowels because they know when they see it, that's likely where the lesions are located," said Suzanne Devkota, PhD, principal investigator and lead author of the study. "But we don't know whether the presence of the fat is making the disease worse or trying to protect the intestines from something."Devkota and a team of investigators performed in-depth molecular examinations of small intestine and fat tissue samples from 11 Crohn's patients who had undergone surgery. Adipose tissue -- commonly known as fat -- is more than an energy storehouse. It is a dynamic endocrine tissue full of immune cells that appear to be triggered in certain cases of inflammatory bowel disease."We found that the adipose tissue is actually responding to bacteria that have migrated out of the patient's damaged intestines and directly into the fat. We believe the 'creeping' migration of the fat around the intestines is intended to try and plug leaks in the diseased organ to prevent the gut bacteria from getting into the bloodstream," Devkota said.But the response that begins as protective apparently has no "off" switch. If the bacteria remains in the fat it will continue to migrate to a possible source of the gut bug. But the presence of the fat may be contributing to the development of severe intestinal scarring, or fibrosis, which occurs in 40% of Crohn's patients. Surgical removal of parts of the small bowel is the only option for many of them and it comes with life-changing consequences. Patients with ulcerative colitis, the other most common IBD, do not develop creeping fat.The data led researchers to a specific microbe responsible for prompting the fat to travel to the small intestine and protectively encase the organ, imperiling its function."We identified a pathogen found in the digestive system, This research could point the way to new therapeutics, Cedars-Sinai experts say."Improving the lives of our IBD patients is the goal of our research. We've identified a specific infectious agent that can trigger a process that makes Crohn's worse. This is a critical step toward the development of therapies that target C. innocuum, allowing us to prevent or minimize the damaging effect of creeping fat," said Stephan R. Targan, MD, director of the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai.Research for this study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number 1R01DK123446-01 and by the Leona M. and Harry B. Helmsley Charitable Trust.Investigators from the University of California, San Diego, the Harvard T.H. Chan School of Public Health and the University of Chicago contributed to this study. | Microbes | 2,020 |
September 28, 2020 | https://www.sciencedaily.com/releases/2020/09/200928155750.htm | How Zika virus degrades essential protein for neurological development via autophagy | In a study published in | "The Zika virus is able to disrupt our cellular mechanisms to create a conducive environment to replicate," explains Yanjin Zhang, associate professor in Veterinary Medicine at UMD. "It upregulates some proteins and downregulates others that have antiviral roles, manipulating and interfering with cells to its own advantage. In this case, it looks like the KPNA2 protein may have some antiviral effects, so the virus uses the natural cellular self-destruction process called autophagy, or self-eating, to get rid of KPNA2."The human body is full of mechanisms to move information and equipment like proteins around, or clear out unnecessary equipment through self-destruct processes like autophagy. In autophagy, cellular components like proteins are marked as damaged, essentially triggering the cell to eat itself to recycle vital ingredients for cell regeneration. However, in this case, the Zika virus wants the protein KPNA2 destroyed for its own benefit."Researchers knew that KPNA2 has important roles in transporting proteins, but we didn't know the mechanism of its turnover until now," says Zhang. "KPNA2 is known to transport important cellular factors needed for development, growth, and cell differentiation during neurological or brain development."Since Zika virus is known to cause infection in pregnant women that can lead to brain deficiencies and congenital defects like microcephaly (a birth defect leading to smaller head and brain size) in newborns, the fact that it degrades this particular protein is important to understanding the development of these defects.Zika virus is a globally mosquito-transmitted virus that has been identified in 87 countries and territories as of 2019 according to the World Health Organization (WHO). While no cases have been reported in the United States in the last few years, the WHO reports a suspected total of over 30,000 cases in the Americas alone in 2018. After the Zika virus epidemic in 2015-2016, the health risk for pregnant mothers and congenital birth defects in newborns became a major public health concern."Zika virus is more of an issue internationally than locally right now," says Zhang, "but as we can see with COVID-19, a global disease can easily become a local concern. Nowadays, it is so easy to travel from one continent to another, and with commercial trade, everything is interlinked. Vectors like mosquitoes can be carried across the world and open new pathways of transmission."The changing climate also plays a role in the spread of infectious diseases like this, explains Zhang. "This is vector-borne or mosquito-borne disease, and as the climate changes, the mosquitoes can reproduce more, and can move farther north and into other areas they may not have been before."Zhang is hopeful, however, that his work will help lead to therapeutic options that can help prevent birth defects caused by Zika virus infection. "Understanding this mechanism is an important step towards understanding how to control the effects of Zika virus, including congenital birth defects," says Zhang. | Microbes | 2,020 |
September 28, 2020 | https://www.sciencedaily.com/releases/2020/09/200928152855.htm | Strong activation of anti-bacterial T cells linked to severe COVID-19 | A type of anti-bacterial T cells, so-called MAIT cells, are strongly activated in people with moderate to severe COVID-19 disease, according to a study by researchers at Karolinska Institutet in Sweden that is published in the journal | "To find potential treatments against COVID-19, it is important to understand in detail how our immune system reacts and, in some cases, perhaps contribute to worsening the disease," says Johan Sandberg, professor at the Department of Medicine, Huddinge, at Karolinska Institutet and the study's corresponding author.T cells are a type of white blood cells that are specialized in recognizing infected cells, and are an essential part of the immune system. About 1 to 5 percent of T cells in the blood of healthy people consist of so-called MAIT cells (mucosa-associated invariant T cells), which are primarily important for controlling bacteria but can also be recruited by the immune system to fight some viral infections.In this study, the researchers wanted to find out which role MAIT cells play in COVID-19 disease pathogenesis. They examined the presence and character of MAIT cells in blood samples from 24 patients admitted to Karolinska University Hospital with moderate to severe COVID-19 disease and compared these with blood samples from 14 healthy controls and 45 individuals who had recovered from COVID-19. Four of the patients died in the hospital.The results show that the number of MAIT cells in the blood decline sharply in patients with moderate or severe COVID-19 and that the remaining cells in circulation are highly activated, which suggests they are engaged in the immune response against SARS-CoV-2. This pattern of reduced number and activation in the blood is stronger for MAIT cells than for other T cells. The researchers also noted that pro-inflammatory MAIT cells accumulated in the airways of COVID-19 patients to a larger degree than in healthy people."Taken together, these analyses indicate that the reduced number of MAIT cells in the blood of COVID-19 patients is at least partly due increased accumulation in the airways," Johan Sandberg says.In convalescent patients, the number of MAIT cells in the blood recovered at least partially in the weeks after disease, which can be important for managing bacterial infections in individuals who have had COVID-19, according to the researchers. In the patients who died, the researchers noted that the MAIT cells tended to be extremely activated with lower expression of the receptor CXCR3 than in those who survived."The findings of our study show that the MAIT cells are highly engaged in the immunological response against COVID-19," Johan Sandberg says. "A likely interpretation is that the characteristics of MAIT cells make them engaged early on in both the systemic immune response and in the local immune response in the airways to which they are recruited from the blood by inflammatory signals. There, they are likely to contribute to the fast, innate immune response against the virus. In some people with COVID-19, the activation of MAIT cells becomes excessive and this correlates with severe disease."This research was supported by the Swedish Research Council, the Swedish Cancer Society, the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, Nordstjernan AB and Karolinska Institutet. | Microbes | 2,020 |
September 24, 2020 | https://www.sciencedaily.com/releases/2020/09/200924141545.htm | Genome of Alexander Fleming's original penicillin-producing mold sequenced | Researchers have sequenced the genome of Alexander Fleming's penicillin mould for the first time and compared it to later versions. | Alexander Fleming famously discovered the first antibiotic, penicillin, in 1928 while working at St Mary's Hospital Medical School, which is now part of Imperial College London. The antibiotic was produced by a mould in the genus Penicillium that accidentally started growing in a Petri dish.Now, researchers from Imperial College London, CABI and the University of Oxford have sequenced the genome of Fleming's original Penicillium strain using samples that were frozen alive more than fifty years ago.The team also used the new genome to compare Fleming's mould with two strains of Penicillium from the US that are used to produce the antibiotic on an industrial scale. The results, published today in Lead researcher Professor Timothy Barraclough, from the Department of Life Sciences at Imperial and the Department of Zoology at Oxford, said: "We originally set out to use Alexander Fleming's fungus for some different experiments, but we realised, to our surprise, that no-one had sequenced the genome of this original Penicillium, despite its historical significance to the field."Although Fleming's mould is famous as the original source of penicillin, industrial production quickly moved to using fungus from mouldy cantaloupes in the US. From these natural beginnings, the Penicillium samples were artificially selected for strains that produce higher volumes of penicillin.The team re-grew Fleming's original Penicillium from a frozen sample kept at the culture collection at CABI and extracted the DNA for sequencing. The resulting genome was compared to the previously published genomes of two industrial strains of Penicillium used later in the US.The researchers looked in particular at two kinds of genes: those encoding the enzymes that the fungus uses to produce penicillin; and those that regulate the enzymes, for example by controlling how many enzymes are made.In both the UK and US strains, the regulatory genes had the same genetic code, but the US strains had more copies of the regulatory genes, helping those strains produce more penicillin.However, the genes coding for penicillin-producing enzymes differed between the strains isolated in the UK and US. The researchers say this shows that wild Penicillium in the UK and US evolved naturally to produce slightly different versions of these enzymes.Moulds like Penicillium produce antibiotics to fight off microbes, and are in a constant arms race as microbes evolve ways to evade these defences. The UK and US strains likely evolved differently to adapt to their local microbes.Microbial evolution is a big problem today, as many are becoming resistant to our antibiotics. Although the researchers say they don't yet know the consequences of the different enzyme sequences in the UK and US strains for the eventual antibiotic, they say it does raise the intriguing prospect of new ways to modify penicillin production.First author Ayush Pathak, from the Department of Life Sciences at Imperial, said: "Our research could help inspire novel solutions to combatting antibiotic resistance. Industrial production of penicillin concentrated on the amount produced, and the steps used to artificially improve production led to changes in numbers of genes."But it is possible that industrial methods might have missed some solutions for optimising penicillin design, and we can learn from natural responses to the evolution of antibiotic resistance." | Microbes | 2,020 |
September 24, 2020 | https://www.sciencedaily.com/releases/2020/09/200924114128.htm | Born to be wild: Fungal highways let bacteria travel in exchange for thiamine | Tiny organisms head out on the highway, looking for adventure like they've ridden straight out of the 1960s rock hit, "Born to Be Wild." Researchers from Japan have discovered that while perhaps not as thrill-seeking, bacteria do indeed travel on fungal highways and pay a toll in return. | In a study published this month in Thiamine (vitamin B1) is essential to the health of almost all living organisms, and is synthesized by bacteria, plants, fungi and some protozoans. Free thiamine is scarce in the environment, and organisms appear to have developed numerous ways of obtaining it."Some species have developed mutually beneficial strategies that allow them to coexist," says lead author of the study Professor Norio Takeshita. "But few strategies that satisfy the need for nutrients and physical niches have been documented. So, we examined the interaction of a fungus and a bacterium to investigate strategies that meet those needs."To do this, the researchers used transcriptomic analyses (i.e., examining all the RNA molecules of an organism), as well as genetic, molecular mass and imaging methods, including live imaging. Stable isotope labeling was used to investigate thiamine transfer from bacteria to the fungus."The bacteria cultured with the fungus traveled along fungal filaments using their flagella," explains Professor Nozomu Obana, senior author. "They dispersed farther with the expansion of the fungal colony than they would have otherwise, suggesting that the fungal filaments supply space for bacteria to migrate, disperse and multiply."The fungus in this study is a type that can synthesize thiamine on its own, but used thiamine produced by the bacteria. Because these bacteria synthesize thiamine extracellularly, neighboring bacteria and fungi in nature could uptake it and use it, saving them the cost of synthesizing it themselves."We're proposing a new mutualistic growth mechanism in bacterial-fungal interactions, in which the bacteria move along the fungal highway and pay thiamine as a toll to the growing fungal filaments," says Professor Takeshita.This research and future studies will contribute to an understanding of selective microbial communication, and live imaging could be used to screen for affinities between bacteria and fungi. Research in this area could be applied to a range of settings from fermentation, biomass degradation, and the promotion of plant growth, as well as plant and human pathogenesis. | Microbes | 2,020 |
September 23, 2020 | https://www.sciencedaily.com/releases/2020/09/200923164601.htm | How microbes in a mother's intestines affect fetal neurodevelopment | During pregnancy in mice, the billions of bacteria and other microbes that live in a mother's intestines regulate key metabolites, small molecules that are important for healthy fetal brain development, UCLA biologists report Sept. 23 in the journal | While the maternal gut microbiota has been associated with abnormalities in the brain function and behavior of offspring -- often in response to factors like infection, a high-fat diet or stress during pregnancy -- scientists had not known until now whether it influenced brain development during critical prenatal periods and in the absence of such environmental challenges.To test the impact the gut microbiata has on the metabolites and other biochemicals that circulate in maternal blood and nurture the rapidly developing fetal brain, the researchers raised mice that were treated with antibiotics to kill gut bacteria, as well as mice that were bred microbe-free in a laboratory."Depleting the maternal gut microbiota, using both methods, similarly disrupted fetal brain development," said the study's lead author, Helen Vuong, a postdoctoral scholar in laboratory of UCLA's Elaine Hsiao.Depleting the maternal gut microbiota altered which genes were turned on in the brains of developing offspring, including many genes involved in forming new axons within neurons, Vuong said. Axons are tiny fibers that link brain cells and enable them to communicate.In particular, axons that connect the brain's thalamus to its cortex were reduced in number and in length, the researchers found."These axons are particularly important for the ability to sense the environment," Vuong said. "Consistent with this, offspring from mothers lacking a gut microbiota had impairments in particular sensory behaviors."The findings indicate that the maternal gut microbiota can promote healthy fetal brain development by regulating metabolites that enter the fetal brain itself, Vuong said."When we measured the types and levels of molecules in the maternal blood, fetal blood and fetal brain, we found that particular metabolites were commonly decreased or missing when the mother was lacking a gut microbiota during pregnancy," she said.The biologists then grew neurons in the presence of these key metabolites. They also introduced these metabolites into the microbiata-depleted pregnant mice."When we grew neurons in the presence of these metabolites, they developed longer axons and greater numbers of axons," Vuong said. "And when we supplemented the pregnant mice with key metabolites that were decreased or missing when the microbiata was depleted, levels of those metabolites were restored in the fetal brain and the impairments in axon development and in offspring behavior were prevented."The gut microbiota has the incredible capability to regulate many biochemicals not only in the pregnant mother but also in the developing fetus and fetal brains," Vuong said. "Our findings also pinpoint select metabolites that promote axon growth."The results suggest that interactions between the microbiota and nervous system begin prenatally through the influence of the maternal gut microbiota on the fetal brain, at least in mice.The applicability of the findings to humans is still unclear, said the study's senior author, Elaine Hsiao, a UCLA associate professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College."We don't know whether and how the findings may apply to humans," said Hsiao, who is also an associate professor of digestive diseases at the David Geffen School of Medicine at UCLA. "However, there are many neurodevelopmental disorders that are believed to be caused by both genetic and environmental risk factors experienced during pregnancy. Our study suggests that maternal gut microbiota during pregnancy should also be considered and further studied as a factor that could potentially influence not only the health of the mother but the health of the developing offspring as well."Hsiao, Vuong and colleagues reported in 2019 that serotonin and drugs that target serotonin, such as antidepressants, can have a major effect on the gut's microbiota. In 2018, Hsiao and her team established a causal link between seizure susceptibility and gut microbiota and identified specific gut bacteria that play an essential role in the anti-seizure effects of the ketogenic diet. | Microbes | 2,020 |
September 23, 2020 | https://www.sciencedaily.com/releases/2020/09/200923124756.htm | Magnetic 'T-Budbots' made from tea plants kill and clean biofilm | Biofilms -- microbial communities that form slimy layers on surfaces -- are difficult to treat and remove, often because the microbes release molecules that block the entry of antibiotics and other therapies. Now, researchers reporting in | Many hospital-acquired infections involve bacterial biofilms that form on catheters, joint prostheses, pacemakers and other implanted devices. These microbial communities, which are often resistant to antibiotics, can slow healing and cause serious medical complications. Current treatment includes repeated high doses of antibiotics, which can have side effects, or in some cases, surgical replacement of the infected device, which is painful and costly. Dipankar Bandyopadhyay and colleagues wanted to develop biocompatible microbots that could be controlled with magnets to destroy biofilms and then scrub away the mess. The team chose The researchers ground some tea buds and isolated porous microparticles. Then, they coated the microparticles' surfaces with magnetite nanoparticles so that they could be controlled by a magnet. Finally, the antibiotic ciprofloxacin was embedded within the porous structures. The researchers showed that the T-Budbots released the antibiotic primarily under acidic conditions, which occur in bacterial infections. The team then added the T-Budbots to bacterial biofilms in dishes and magnetically steered them. The microbots penetrated the biofilm, killed the bacteria and cleaned the debris away, leaving a clear path in their wake. Degraded remnants of the biofilm adhered to the microbots' surfaces. The researchers note that this was a proof-of-concept study, and further optimization is needed before the T-Budbots could be deployed to destroy biofilms in the human body.Video: | Microbes | 2,020 |
September 22, 2020 | https://www.sciencedaily.com/releases/2020/09/200922112236.htm | Living in an anoxic world: Microbes using arsenic are a link to early life | Much of life on planet Earth today relies on oxygen to exist, but before oxygen was present on our blue planet, lifeforms likely used arsenic instead. These findings are detailed in research published today in | A key component of the oxygen cycle is where plants and some types of bacteria essentially take sunlight, water and COLight-driven, photosynthetic organisms appear in the fossil record as layered carbonate rocks called stromatolites dating to around 3.7 billion years ago, says Visscher. Stromatolite mats are deposited over the eons by microbial ecosystems, with each layer holding clues about life at that time. There are contemporary examples of microbes that photosynthesize in the absence of oxygen using a variety of elements to complete the process, however it is not clear how this happened in the earliest life forms.Theories as to how life's processes functioned in the absence of oxygen have mostly relied on hydrogen, sulfur, or iron as the elements that ferried electrons around to fulfill the metabolic needs of organisms.Visscher explains these theories are contested, for example photosynthesis is possible with iron but researchers do not find evidence of that in the fossil record before oxygen appeared some 2.4 billion years ago. Hydrogen is mentioned yet the energetics and competition for hydrogen between different microbes shows it is highly unfeasible.Arsenic is another theoretical possibility, and evidence for that was found in 2008. Visscher says the link with arsenic was strengthened in 2014 when he and colleagues found evidence of arsenic-based photosynthesis in deep time. To further support their theory, the researchers needed to find a modern analog to study the biogeochemistry and element cycling.Finding an analog to the conditions on early Earth is a challenge for a number of reasons, besides the fact that oxygen is abundant on modern earth. For instance, the evidence shows early microbes captured atmospheric carbon and produced organic matter at a time when volcanic eruptions were frequent, UV light was intense in the absence of the ozone layer, and oceans were essentially a toxic soup.Another challenging aspect of working within the fossil record, especially those as ancient as some stromatolites, is that there are few left due to the cycling of rock as continents move and time marches on. However, a breakthrough happened when the team discovered an active microbial mat, currently existing in the harsh conditions in Laguna La Brava in the Atacama Desert in Chile.The mats have not been studied previously but present an otherworldly set of conditions, like those of early Earth. The mats are in a unique environment which leaves them in a permanent oxygen-free state at high altitude where they are exposed to wild, daily temperature swings, and high UV conditions. The mats serve as powerful and informative tools for truly understanding life in the conditions of early Earth.Visscher explains, "We started working in Chile, where I found a blood red river. The red sediments are made up by anoxogenic photosynthetic bacteria. The water is very high in arsenic as well. The water that flows over the mats contains hydrogen sulfide that is volcanic in origin and it flows very rapidly over these mats. There is absolutely no oxygen."The team also showed that the mats were making carbonate deposits and creating a new generation of stromatolites. The carbonate materials also showed evidence for arsenic cycling -- that arsenic is serving as a vehicle for electrons -- proving that the microbes are actively metabolizing arsenic much like oxygen in modern systems. Visscher says that these findings, along with the fossil evidence gives a strong indication of what was seen on early earth."Arsenic-based life has been a question in terms of does it have biological role or is it just a toxic compound?" says Visscher. That question appears to be answered, "I have been working with microbial mats for about 35 years or so. This is the only system on Earth where I could find a microbial mat that worked absolutely in the absence of oxygen."Visscher points out that an important tool they used to perform this research is similar to one onboard the Mars Perseverance rover, currently en route to Mars."In looking for evidence of life on Mars they will be looking at iron and probably they should be looking at arsenic also." | Microbes | 2,020 |
September 22, 2020 | https://www.sciencedaily.com/releases/2020/09/200922102427.htm | Researchers find new way to protect plants from fungal infection | Widespread fungal disease in plants can be controlled with a commercially available chemical that has been primarily used in medicine until now. This discovery was made by scientists from Martin Luther University Halle-Wittenberg (MLU) and the University of the State of Paraná in Brazil. In a comprehensive experiment the team has uncovered a new metabolic pathway that can be disrupted with this chemical, thus preventing many known plant fungi from invading the host plant. The team reported on their study in the scientific journal | The fungus Colletotrichum graminicola is prevalent around the world. It infects maize, causing anthracnose, a disease that causes the plant's leaves to turn yellow at first and then ultimately to succumb to toxins. The fungus multiplies through spores that initially land on the surface of the plant. There they find rather inhospitable conditions: a lack of most of the nutrients that fungi need to develop -- in particular nitrogen. "The only option they have is to break down some of their own nitrogen-containing molecules, for instance purines, the building blocks of DNA or RNA," explains plant pathologist Professor Holger Deising from MLU.The researchers on Deising's team have found a way to impede this transitional phase which the fungus relies on. To do this, the team administered acetohydroxamic acid onto the plants, a substance also used to treat harmful bacteria in the human stomach, and which is known to inhibit the breakdown of urea. "The acid prevents the harmful fungi from penetrating into the plants and from becoming infectious," says Deising.The team also tested whether the findings from The scientists conducted extensive experiments in order to come to their conclusions. They wanted to understand the molecular details of how the fungus manages to obtain nitrogen at the onset of the infection. First, they generated a series of random mutations in the genome of the fungus | Microbes | 2,020 |
September 18, 2020 | https://www.sciencedaily.com/releases/2020/09/200918104235.htm | Mosquito-borne viruses linked to stroke | A deadly combination of two mosquito-borne viruses may be a trigger for stroke, new research published in the | University of Liverpool researchers and Brazilian collaborators have been investigating the link between neurological disease and infection with the viruses Zika and chikungunya. These viruses, which mostly circulate in the tropics, cause large outbreaks of rash and fever in places like Brazil and India. Zika is widely known to cause brain damage in babies following infection in pregnancy, but the new research shows it can also cause nervous system disease in adults.The study of 201 adults with new onset neurological disease, treated in Brazil during the 2015Zika and 2016 chikungunya epidemics, is the largest of its kind to describe the neurological features of infection for several arboviruses circulating at the same time.The new research shows that each virus can cause a range of neurological problems. Zika was especially likely to cause Guillain-Barre syndrome, in which the nerves in the arms and legs are damaged. Chikungunya was more likely to cause inflammation and swelling in the brain (encephalitis) and spinal cord (myelitis). However, stroke, which could be caused by either virus alone, was more likely to occur in patients infected with the two viruses together.Stroke occurs when one of the arteries supplying blood to the brain becomes blocked. The risk of stroke is known to be increased after some types of viral infection, like varicella zoster virus, which causes chickenpox and shingles, and HIV. Stroke is also being recognised increasingly as a complication of COVID-19. This has important implications for the investigation and management of patients with viral infection, as well as for understanding the mechanisms of disease.In total 1410 patients were screened and 201 recruited over a two-year period at Hospital da Restauração in Recife, Brazil. Comprehensive PCR and antibody testing for viruses was carried out in Fiocruz laboratories.Of the 201 patients admitted with suspected neurological disease linked to Zika, chikungunya or both, 148 had confirmation of infection on laboratory testing, around a third of whom had infection with more than one virus.The median age of patients was 48, and just over half the patients were female. Only around 10% patients had fully recovered at discharge, with many having ongoing issues like weakness, seizures, and problems in brain function.Of the stroke patients, who were aged 67 on average, around two thirds had infection with more than one virus. Many of the people who had a stroke had other stroke risk factors, such as high blood pressure, indicating that stroke following Zika and chikungunya viral infection may most often be seen in those who are already high risk.Dr Maria Lúcia Brito Ferreira, neurologist and head of department at Hospital da Restauração, leading the Brazilian team said: "Zika infection most often causes a syndrome of rash and fever without many long-term consequences, but these neurological complications -- although rare -- can require intensive care support in hospital, often result in disability, and may cause death."Dr Suzannah Lant, a Clinical Research Fellow at the University of Liverpool, who worked on the study explained: "Our study highlights the potential effects of viral infection on the brain, with complications like stroke. This is relevant to Zika and chikungunya, but also to our understanding of other viruses, such as COVID-19, which is increasingly being linked to neurological complications."Senior author Professor Tom Solomon, Director of the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool said: "Although the world's attention is currently focused on COVID-19, other viruses that recently emerged, such as Zika and chikungunya, are continuing to circulate and cause problems. We need to understand more about why some viruses trigger stroke, so that we can try and prevent this happening in the future."The researchers are supported by grants from FACEPE, ZikaPLAN (as part of EU Horizon 2020), the Medical Research Council, Wellcome Trust, and National Institute for Health Research. | Microbes | 2,020 |
September 17, 2020 | https://www.sciencedaily.com/releases/2020/09/200917181240.htm | New high-speed test shows how antibiotics combine to kill bacteria | Researchers at Uppsala University have developed a new method to determine -- rapidly, easily and cheaply -- how effective two antibiotics combined can be in stopping bacterial growth. The new method is simple for laboratories to use and can provide greater scope for customising treatment of bacterial infections. The study is published in | Combinations of antimicrobial agents are invariably prescribed for certain infectious diseases, such as tuberculosis, HIV and malaria. Bacterial infections that are not readily treatable, such as those affecting cardiac valves and prostheses, and lung infections in cystic fibrosis, are also usually subjected to a combination of antibiotics. The effect sought, "synergism," means that the joint action of the combined agents is more effective than could in fact have been expected, based on the efficacy of the separate agents. In contrast, the opposite phenomenon -- that is, two antibiotics counteracting each other's effects ("antagonism") -- is undesirable. However, knowing what the combined effect will be is not always easy.With the newly developed method known as CombiANT (combinations of antibiotics), interactions between various antibiotics can be tested on agar plates and results obtained in 24 hours. The lead author of the study, Nikos Fatsis-Kavalopoulos, developed the method at Uppsala University. It is based on creating a "concentration gradient" of antibiotics that have been cast into an agar plate, using a 3D-printed plastic disc.On the agar plate, bacteria that have been isolated from an individual patient are then cultured to see how they react to different combinations of antibiotics.In their study, the researchers investigated E. coli bacteria isolated from urinary tract infections. Different cultures of E. coli proved not to react in the same way to specific antibiotic combinations. A combination of antibiotics that had synergistic effects on most cultures brought about antagonism in some, with the result that the treatment for the latter group was inferior."This result may be of great clinical importance. Consequently, instead of assuming that synergistic and antagonistic interactions are equal for all bacterial isolates, we test individually every isolate taken from an infected patient," says Dan I. Andersson, Professor of Medical Bacteriology at Uppsala University, who is primarily responsible for the study.Customising the drug combo in this way may be crucially important in achieving high efficacy in the treatment of infections. Being a simple, low-cost method, it is also easy to introduce and use in health care. | Microbes | 2,020 |
September 17, 2020 | https://www.sciencedaily.com/releases/2020/09/200917105326.htm | Scientists uncover the structural mechanism of coronavirus receptor binding | The spike protein on the surface of the SARS-CoV-2 coronavirus can adopt at least ten distinct structural states, when in contact with the human virus receptor ACE2, according to research from the Francis Crick Institute published in | This new insight into the mechanism of infection will equip research groups with the understanding needed to inform studies into vaccines and treatments.The surface of SARS-CoV-2, the virus that causes COVID-19, is covered in proteins called spikes, which enable the virus to infect human cells. The infection begins when a spike protein binds with ACE2 cell surface receptors and, at later stages, catalyses the release of the virus genome into the cell.However, the exact nature of the ACE2 binding to the SARS-CoV-2 spike remains unknown.In the first study to examine the binding mechanism between ACE2 and the spike protein in its entirety, researchers in the Crick's Structural Biology of Disease Processes Laboratory, have characterised ten distinct structures that are associated with different stages of receptor binding and infection.The team incubated a mixture of spike protein and ACE2 before trapping different forms of the protein by rapid freezing in liquid ethane. They examined these samples using cryo-electron microscopy, obtaining tens of thousands of high-resolution images of the different binding stages.They observed that the spike protein exists as a mixture of closed and open structures., Following ACE2 binding at a single open site, the spike protein becomes more open, leading to a series of favourable conformational changes, priming it for additional binding. Once the spike is bound to ACE2 at all three of its binding sites, its central core becomes exposed, which may help the virus to fuse to the cell membrane, permitting infection."By examining the binding event in its entirety, we've been able to characterise spike structures that are unique to SARS-CoV-2," says Donald Benton, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick."We can see that as the spike becomes more open, the stability of the protein will reduce, which may increase the ability of the protein to carry out membrane fusion, allowing infection."The researchers hope that the more we can uncover about how SARS-CoV-2 differs from other coronaviruses, the more targeted we can be with the development of new treatments and vaccines.Antoni Wrobel, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick, says: "As we unravel the mechanism of the earliest stages of infection, we could expose new targets for treatments or understand which currently available anti-viral treatments are more likely to work."Steve Gamblin, group leader of the Structural Biology of Disease Processes Laboratory at the Crick says: "There's so much we still don't know about SARS-CoV-2, but its basic biology contains the clues to managing this pandemic."By understanding what makes this virus distinctive, researchers could expose weaknesses to exploit."The team are continuing to examine the structures of spikes of SARS-CoV-2 and related coronaviruses in other species to better understand the mechanisms of viral infection and evolution. | Microbes | 2,020 |
September 17, 2020 | https://www.sciencedaily.com/releases/2020/09/200917135522.htm | Social distancing and microbial health | Social distancing is a key component of the expert-recommended strategy to reduce the spread of COVID-19. According to the World Health Organization, the SARS-CoV-2 virus passes from person to person primarily through saliva or airborne respiratory droplets. Protective precautions like wearing masks, washing hands, and avoiding close contact with other people can prevent the spread of droplets. | Avoiding contact with others, however, may have repercussions in a person's gut microbiome. In a perspective published this week in "Our behaviors have consequences," said lead author Teresa Nogueira, Ph.D., microbiologist at the National Institute for Agrarian and Veterinary Research and Centre for Ecology, Evolution and Environmental Changes at the University of Lisbon. "We are doing social distancing, which makes sense during the pandemic. But in the long term, social distancing can have consequences on the biodiversity of our microbiota."In the paper, Nogueira and her colleagues highlight 2 critical ways to look for the effect of social distancing on the microbiome. One may be harmful, and the other helpful, leading the authors to describe the effects as a "double-edged sword."First, they worry that social distancing may worsen the prognosis for individuals with many diseases, including COVID-19. Their hypothesis is based not on new findings, but on drawing conclusions from previous ones. Recent studies connect social isolation to less bacterial diversity. Extreme lack of diversity can lead to an imbalance called dysbiosis, which is associated with reduced numbers of protective bacteria. Previous studies have connected dysbiosis to higher risk of opportunistic infections; it's also been shown to increase the risk of influenza infections in the lung. Preliminary studies from the last few months similarly suggest that a person's microbiota influences their response to COVID-19, and that hospitalized COVID-19 patients do face increased risk of dysbiosis .Given what's known about the virus and the microbiome, Nogueira and her colleagues hypothesize that social distancing favors dysbiosis and thus worsens a person's response to COVID-19. It could produce a loop, where dysbiosis triggers poorer responses, which leads to more widespread social distancing, which can exacerbate dysbiosis.But, she cautions, rigorous studies haven't yet been done to support this hypothesis.The second way that social distancing may influence the microbiome is by limiting the transmission of antibiotic resistant microbes between people and the exchange of resistance genes between microbes. Taking antibiotics leads to an increase in antibiotic resistance genes among a person's microbiota. Recent studies by Nogueira's group, however, show that the diversity of these genes increases in time by spreading from person to person. Social distancing limits personal contact, which means it likely limits the transmission of antibacterial resistance as well, Nogueira said."In situations where people avoid one another, we would expect to break this transmission," she said. "In these populations, the resistant bacteria tend to disappear over time." However, as in the case of the connection with dysbiosis, she said that studies haven't rigorously demonstrated that social distancing will reduce antibiotic resistance.Recent years have shown that the microbiota plays a critical role in many aspects of human health, and the authors of the mSphere perspective urge researchers to better probe how the bacterial balance may be affected by social distancing in the short and long term."We're not suggesting any changes to control strategies," Nogueira said. "We want to ask the scientists working in the field to check for this. This is the window of opportunity to do so." | Microbes | 2,020 |
September 16, 2020 | https://www.sciencedaily.com/releases/2020/09/200916131101.htm | Epidemics and pandemics can exacerbate xenophobia, bigotry | When viruses, parasites and other pathogens spread, humans and other animals tend to hunker down with immediate family and peer groups to avoid outsiders as much as possible. | But could these instincts, developed to protect us from illnesses, generalize into avoidance of healthy individuals who simply look, speak or live differently?Jessica Stephenson, an assistant professor in the Department of Biological Sciences in the Kenneth P. Dietrich School of Arts and Sciences, coauthored a paper exploring the answer, which was recently published in the Proceedings of the Royal Society of London, Series B.One example noted in the study showed that black garden ants exposed to a fungus clustered together in groups much smaller than researchers could predict by chance, which effectively limited the spread of disease. Similar behaviors seen among 19 non-human primate species were also credited for lowering direct spread of parasites.Human beings share these same biological impulses to separate into modular social groups. However, when pathogens are spreading, humans tend to also adopt a set of behaviors that are "hypervigilant and particularly error prone," the researchers wrote."It's interesting and really disappointing," Stephenson said. And as COVID-19 continues its spread, humans are even more susceptible to the impulse."During epidemics, humans tend to become overly sensitive, so any sort of physical abnormality that somebody has suddenly becomes a potential indicator of infection. We become much more bigoted, we pay way more attention to things that differentiate people from what we perceive as our own phenotype. People who look different from us and sound different from us, which, of course, leads to a lot more xenophobia," said Stephenson, who runs Stephenson Lab of Disease Ecology and Evolutionary Parasitology at Pitt.A prior Stephenson study published in The Royal Society Biology Letters in November 2019 outlined how individuals differ in their response to potential contagion. In both humans and the guppies she studied, the individuals most susceptible to the disease showed the strongest avoidance.During that study, male guppies were placed in a large tank, flanked by a smaller one containing a group of three female guppies that were visibly infected with parasites. Many males preferred to spend time near the female guppies, despite the risk of contagion. But some male guppies strongly avoided the other fish. The socially distant male guppies were later shown to be highly susceptible to worm infections.Stephenson said human beings are generally "normal social animals in many of our behavioral responses to infectious diseases." But, if humans choose social urges over infection control, efforts such as global disease surveillance and centralized public health responses could be wasted, she said."That the vast majority of our species has largely squandered the potential payoffs of these benefits is again consistent with other social animals: the cost of social distancing itself can outweigh the cost of contracting the disease," Stephenson said.But humans have a leg up on fish: access to information and means of virtual communication. Stephenson's 2020 study noted that synchronous communication, virtual or not, can mitigate some of the effects of confinement. Computer-mediated discussions can also promote more equal participation from minority groups."For some, no amount of Zoom and FaceTime can make up for the lost benefits of social interactions. These frustrating, if wholly natural, behavioral decisions will result in the persistence of COVID-19 until the advent of perhaps our greatest advantage over other species facing emerging infectious diseases: vaccination.""We shouldn't discriminate against different groups in our social distancing, or in our efforts to work together to beat the virus," she added. "But I think our natural, evolved tendencies would be to associate only within our ingroups. We have to fight that natural antipathy towards people who differ from ourselves, and not shut down." | Microbes | 2,020 |
September 15, 2020 | https://www.sciencedaily.com/releases/2020/09/200915105959.htm | Tiny protein motor fuels bacterial movement | There are billions of bacteria around us and in our bodies, most of which are harmless or even helpful. But some bacteria such as E. coli and salmonella can cause infections. The ability to swim can help bacteria to seek out nutrients or to colonize parts of the body and cause infection. | Researchers from the Faculty of Health and Medical Sciences, University of Copenhagen, have now provided fundamental insight into how this bacterial movement is powered, solving a yearlong mystery within the field.'A lot of bacteria can move, or swim, because they have long threads, also known as flagella, which they can use to propel themselves forward. They do this by rotating these threads. The rotation is powered by a rotary motor, which again is powered by a protein complex known as the stator unit. This is all well known within our field. What we now show is how this stator unit powers the motor, which has been a mystery so far', says Associate Professor and Group Leader Nicholas Taylor, Novo Nordisk Foundation Center for Protein Research.Quite surprisingly, the team shows that the stator unit itself is in fact also a tiny rotary motor. This tiny motor powers the large motor, which makes the threads rotate, causing the bacteria to move. The results contradict existing theories on the mechanism of the stator unit, and this new knowledge might be useful in the fight against bacteria-based diseases.'Most researchers, including ourselves, actually thought that the technical mechanism and the architecture of the stator unit was quite different to what our study shows. Knowing the actual composition and function of this unit paves the way for therapeutic purposes. When we know what makes bacteria move, we might also be able to inhibit this movement and thereby stop it from spreading', says Nicholas Taylor.Cryo-electron microscopy reveals the architecture of the motorThe researchers determined the structure of the stator unit complex by using cryo-electron microscopy. Working with this technique, they were able to elucidate its architecture, see how it is activated and provide a detailed model for how it powers rotation of the flagellar motor."The motor consists of two proteins: MotA and MotB. The MotB protein is anchored to the cell wall, and is surrounded by MotA proteins, which, upon dispersion of the ion motive force, rotates around MotB. The rotation of MotA in turn powers rotation of the large bacteria motor," says Nicholas Taylor."Furthermore, our model shows how the stator unit can power rotation of the bacterial flagellar motor in both directions, which is crucial for the bacteria to change their swimming direction. Without direction change, bacteria would only be able to swim straight in one direction."Next step for the group is to find out if it is possible to inhibit the stator units using chemical compounds, which could have antibiotic effects. | Microbes | 2,020 |
September 15, 2020 | https://www.sciencedaily.com/releases/2020/09/200915105932.htm | Rising temperatures could shift US West Nile virus transmission | West Nile virus spreads most efficiently in the US at temperatures between 24-25 degrees Celsius (75.2-77 degrees Fahrenheit), a new study published today in | The results suggest that climate change could lead to the increased spread of West Nile virus in some places, while potentially causing a decrease in others, and provide insight on where and when these changes might occur."As the climate warms, it is critical to understand how temperature changes will affect the transmission of mosquito-borne diseases," says lead author Marta Shocket, who was a Postdoctoral Fellow at Stanford University, California, US, at the time the study was carried out, and is now a Postdoctoral Researcher at the University of California, Los Angeles, US.To do this, Shocket and her colleagues developed models to assess the impact of temperature on six mosquito-borne viruses, four of which occur in the US. These viruses -- the West Nile, St. Louis Encephalitis, Eastern and Western Equine Encephalitis, Sindbis, and Rift Valley fever viruses -- were grouped together for this study as they share some of the same species of mosquito carriers.The models used laboratory experiments that measured how different temperatures affect the mosquitoes' survival, biting rate, reproduction, development and ability to transmit the virus. The team validated their West Nile model using data on human virus transmission in the US. They found that West Nile virus is transmitted most readily at moderate temperatures, while extreme temperatures limit where its mosquito carriers could live and successfully transmit the virus."Most of the viruses covered in this work are from more temperate areas than more commonly studied tropical diseases," Shocket explains. "We compared these results to those of tropical diseases like malaria and dengue and found that the optimal temperatures and cold thermal limits for virus spread are cooler. This means the viruses spread more efficiently at cooler temperatures compared to more tropical diseases, as you would expect."The results suggest that mosquito-borne diseases could take a greater toll in the US as temperatures rise, especially as most of the population (70%) lives in places that are currently below the optimal temperature and will likely see increased transmission with climate warming. This is compared to 30% of the population who live in places where summer temperatures are above the optimal temperature, meaning transmission will likely decrease with climate warming. Temperature increases could also extend virus transmission seasons earlier into the Spring and later into the Fall."Climate change is poised to increase the transmission of West Nile and other mosquito-borne viruses in much of the US," concludes senior author Erin Mordecai, Assistant Professor of Biology at Stanford University. "But these diseases also depend on human contact with mosquitoes that also contact wildlife, so factors like human land use, mosquito control, mosquito and virus adaptations, and the emergence of new viruses make predicting the future of mosquito-borne disease a challenge." | Microbes | 2,020 |
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