Tag Archives: Microbio News

AI-Powered Breakthrough for Improved At-Home Hepatitis and COVID-19 Testing

Researchers at the University of Florida are using AI to develop an improved at-home test for diseases like hepatitis C and COVID-19. They have combined RT-LAMP and CRISPR technologies to create a simplified, one-pot reaction test called SPLENDID, which has demonstrated 97% accuracy for detecting SARS-CoV-2 and 95% accuracy for the most common strain of hepatitis C.

Going beyond pregnancy and COVID-19, the world could someday soon come to rely on at-home tests for many diseases thanks in part to AI-fueled improvements.

University of Florida (UF) scientists have used artificial intelligence tools to simplify a test that works for both hepatitis C and SARS-CoV-2, the virus that causes COVID-19. The simplified test happens in one small test tube in just a few minutes. With further refinement, it could come to doctor’s offices soon and, one day, even home tests that are as easy as a pregnancy test.

“We are trying to build a home-based test that is as reliable as a lab-based test,” said Piyush Jain, a UF professor of chemical engineering who led the latest research. “We are trying to make the test simple, eliminate the need for expensive equipment, and provide results in just 10 to 20 minutes.”

To accomplish those goals, Jain’s group is innovating on a system known as a one-pot reaction, because the entire test happens in one small test tube. These tests, based on a technology known as RT-LAMP, can amplify small portions of a virus’s genome and produce a visible signal when it detects the virus. Reading these tests can be as simple as looking for a blue color or using a small device that detects a change in the test tube.

The FDA has approved some at-home, one-pot tests for COVID-19, as a part of the emergency use authorization, but they have a relatively high false positive rate, meaning they aren’t as reliable as they could be.

“We are combining another technology called CRISPR to determine the difference between a false positive and a true positive,” Jain said.

CRISPR has become known in the biotech world for its ability to drive rapid genetic engineering improvements, which have the potential to one day cure inherited diseases by repairing genomes. Jain’s group relies on the CRISPR system’s ability to home in on particular genetic sequences. Only if the sequence for, say, the hepatitis virus is really present will the test show a positive result. 

The only problem? The RT-LAMP technology requires a temperature of 150 degrees F, while CRISPR works best at 100 degrees. That difference makes tests far more complicated requiring two separate reactions– too complicated for at-home use. Jain’s team has been trying to bridge this gap by developing a CRISPR system that can withstand higher temperatures.

From a heat-loving species of bacteria, the researchers recently discovered a CRISPR enzyme that thrives at 140 degrees. In their latest work, Jain’s group turned to AI tools to analyze this enzyme and discover how they could make it survive at 150 degrees. The AI programs suggested a few dozen changes to the enzyme, which Jain’s group tested in the lab. They eventually found four changes to the enzyme that let it work at 150 degrees.

“It’s very challenging for any human to do this kind of analysis on an enzyme. We didn’t have to spend years, we could make these improvements in months,” Jain said. “With everything working at the same temperature, now we are able to combine everything in a true one-pot reaction, we call SPLENDID.”

The team verified their simplified SPLENDID test on clinical samples from patients with hepatitis C or COVID-19. The test was 97% accurate for SARS-CoV-2 and 95% accurate for the most prevalent version of the hepatitis C virus found globally. Although it didn’t work well against all other less predominant versions of the hepatitis C virus, straightforward changes to the test should quickly improve its accuracy, Jain says. His team published their findings on May 8 in the journal Cell Reports Medicine.

The work was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in hopes of developing simple tests for viruses like hepatitis C so they can be identified and treated early, when treatments work best. Jain’s group will now work to refine the test, improve its ability to distinguish between hepatitis C strains and verify it in hospital settings in hopes of one day providing at-home tests as well.

Reference: “Engineering highly thermostable Cas12b via de novo structural analyses for one-pot detection of nucleic acids” by Long T. Nguyen, Santosh R. Rananaware, Lilia G. Yang, Nicolas C. Macaluso, Julio E. Ocana-Ortiz, Katelyn S. Meister, Brianna L.M. Pizzano, Luke Samuel W. Sandoval, Raymond C. Hautamaki, Zoe R. Fang, Sara M. Joseph, Grace M. Shoemaker, Dylan R. Carman, Liwei Chang, Noah R. Rakestraw, Jon F. Zachary, Sebastian Guerra, Alberto Perez and Piyush K. Jain, 8 May 2023, Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2023.101037

Ancient viruses discovered in coral symbionts’ DNA

An international team of marine biologists has discovered the remnants of ancient RNA viruses embedded in the DNA of symbiotic organisms living inside reef-building corals.

The RNA fragments are from viruses that infected the symbionts as long ago as 160 million years. The discovery is described in an open-access study published this week in the Nature journal Communications Biology, and it could help scientists understand how corals and their partners fight off viral infections today. But it was a surprising find because most RNA viruses are not known for embedding themselves in the DNA of organisms they infect.

The research showed that endogenous viral elements, or EVEs, appear widely in the genomes of coral symbionts. Known as dinoflagellates, the single-celled algae live inside corals and provide them with their dramatic colors. The EVE discovery underscores recent observations that viruses other than retroviruses can integrate fragments of their genetic code into their hosts’ genomes.

“So why did it get in there?” asked study co-author Adrienne Correa of Rice University. “It could just be an accident, but people are starting to find that these ‘accidents’ are more frequent than scientists had previously believed, and they’ve been found across all kinds of hosts, from bats to ants to plants to algae.”

That an RNA virus appears at all in coral symbionts was also a surprise.

“This is what made this project so interesting to me,” said study lead author Alex Veglia, a graduate student in Correa’s research group. “There’s really no reason, based on what we know, for this virus to be in the symbionts’ genome.”

The study was supported by the Tara Ocean Foundation and the National Science Foundation and led by Correa, Veglia and two scientists from Oregon State University, postdoctoral scholar Kalia Bistolas and marine ecologist Rebecca Vega Thurber. The research provides clues that can help scientists better understand the ecological and economic impact of viruses on reef health.

The researchers did not find EVEs from RNA viruses in samples of filtered seawater or in the genomes of dinoflagellate-free stony corals, hydrocorals or jellyfish. But EVEs were pervasive in coral symbionts that were collected from dozens of coral reef sites, meaning the pathogenic viruses were — and probably remain — picky about their target hosts.

“There’s a huge diversity of viruses on the planet,” said Correa, an assistant professor of biosciences. “Some we know a lot about, but most viruses haven’t been characterized. We might be able to detect them, but we don’t know who serves as their hosts.”

She said viruses, including retroviruses, have many ways to replicate by infecting hosts. “One reason our study is cool is because this RNA virus is not a retrovirus,” Correa said. “Given that, you wouldn’t expect it to integrate into host DNA.

“For quite a few years, we’ve seen a ton of viruses in coral colonies, but it’s been hard to tell for sure what they were infecting,” Correa said. “So this is likely the best, most concrete information we have for the actual host of a coral colony-associated virus. Now we can start asking why the symbiont keeps that DNA, or part of the genome. Why wasn’t it lost a long time ago?”

The discovery that the EVEs have been conserved for millions of years suggests they may somehow be beneficial to the coral symbionts and that there is some kind of mechanism that drives the genomic integration of the EVEs.

“There are a lot of avenues we can pursue next, like whether these elements are being used for antiviral mechanisms within dinoflagellates, and how they are likely to affect reef health, especially as oceans warm,” Veglia said.

“If we’re dealing with an increase in the temperature of seawater, is it more likely that Symbiodiniaceae species will contain this endogenous viral element? Does having EVEs in their genomes improve their odds of fighting off infections from contemporary RNA viruses?” he said.

“In another paper, we showed there was an increase in RNA viral infections when corals underwent thermal stress. So there are a lot of moving parts. And this is another good piece of that puzzle.”

Correa said, “We can’t assume that this virus has a negative effect. But at the same time, it does look like it’s becoming more productive under these temperature stress conditions.”

Thurber is the Emile F. Pernot Distinguished Professor in Oregon State’s Department of Microbiology.

The study included more than 20 co-authors from the University of Konstanz, Germany; the Institute of Microbiology and Swiss Institute of Bioinformatics, Zürich; the University of Perpignan, France; the Scientific Center of Monaco; the Université Paris-Saclay, Evry, France; the Tara Ocean Foundation, Paris; the University of Maine; Sorbonne University, France; the University of Tsukuba, Japan; Paris Science and Letters University, France; the University of Paris-Saclay; the Weizmann Institute of Science, Rehovot, Israel; Côte d’Azur University, Nice, France; the European Bioinformatics Institute, University of Cambridge, England; Ohio State University; and the National University of Ireland, Galway.

National Science Foundation support was provided by three grants (2145472, 2025457, 1907184).

  • Alex J. Veglia, Kalia S. I. Bistolas, Christian R. Voolstra, Benjamin C. C. Hume, Hans-Joachim Ruscheweyh, Serge Planes, Denis Allemand, Emilie Boissin, Patrick Wincker, Julie Poulain, Clémentine Moulin, Guillaume Bourdin, Guillaume Iwankow, Sarah Romac, Sylvain Agostini, Bernard Banaigs, Emmanuel Boss, Chris Bowler, Colomban de Vargas, Eric Douville, Michel Flores, Didier Forcioli, Paola Furla, Pierre E. Galand, Eric Gilson, Fabien Lombard, Stéphane Pesant, Stéphanie Reynaud, Shinichi Sunagawa, Olivier P. Thomas, Romain Troublé, Didier Zoccola, Adrienne M. S. Correa, Rebecca L. Vega Thurber. Endogenous viral elements reveal associations between a non-retroviral RNA virus and symbiotic dinoflagellate genomes. Communications Biology, 2023; 6 (1) DOI: 10.1038/s42003-023-04917-9
  • Rice University

    NIH Scientists Discover Protein Behind Rare Genetic Skin Disorder

    Genome sequencing reveals genetic basis for disabling pansclerotic morphea, a severe inflammatory disease.

    Researchers at the National Institutes of Health (NIH) and their colleagues have identified genomic variants that cause a rare and severe inflammatory skin disorder, known as disabling pansclerotic morphea, and have found a potential treatment. Scientists discovered that people with the disorder have an overactive version of a protein called STAT4, which regulates inflammation and wound healing. The work also identified a drug that targets an important feedback loop controlled by the STAT4 protein and significantly improves symptoms in these patients. The results were published in the New England Journal of Medicine.

    The study was led by researchers at the National Human Genome Research Institute (NHGRI), part of NIH, in collaboration with researchers from the University of California, San Diego (UCSD) and the University of Pittsburgh. Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases, both part of NIH, also participated in the study.

    Only a handful of patients have been diagnosed with disabling pansclerotic morphea, a disorder first described in the medical literature around 100 years ago. The disorder causes severe skin lesions and poor wound healing, leading to deep scarring of all layers of the skin and muscles. The muscles eventually harden and break down while the joints stiffen, leading to reduced mobility. Because the disorder is so rare, its genetic cause had not been identified until now.

    “Researchers previously thought that this disorder was caused by the immune system attacking the skin,” said Sarah Blackstone, a predoctoral fellow within NHGRI’s Inflammatory Disease Section, a medical student at the University of South Dakota and co-first author of the study. “However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea.”

    The researchers used genome sequencing to study four individuals with disabling pansclerotic morphea and found that all four have genomic variants in the STAT4 gene. The STAT4 gene encodes a type of protein that helps turn genes on and off, known as a transcription factor. The STAT4 protein not only plays a role in fighting infections but also controls important aspects of wound healing in the skin.

    The scientists found that the STAT4 genomic variants result in an overactive STAT4 protein in these four patients, creating a positive feedback loop of inflammation and impaired wound healing that worsens over time. To stop this harmful feedback loop, they targeted another protein in the inflammatory pathway that interacts with the STAT4 molecule and is called Janus kinase, also known as JAK. When the researchers treated the patients with a JAK-inhibiting drug called ruxolitinib, the patients’ rashes and ulcers dramatically improved.

    “So far, there has not been a standard treatment for this disorder because it’s so rare and not well-understood. However, our study gives an important new treatment option for these patients,” said Blackstone.

    Existing treatments for disabling pansclerotic morphea are designed to halt the progression of the disorder, but previous therapies have been mostly ineffective, often with severe side effects. People with the disorder typically don’t live more than 10 years after their diagnosis.

    The study suggests that ruxolitinib could be an effective treatment for patients with this disorder. Ruxolitinib is part of a broader class of drugs called JAK inhibitors, which are commonly used to treat arthritis, eczema, ulcerative colitis, and other chronic inflammatory diseases.

    “The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver, or bone marrow,” said Dan Kastner, M.D., Ph.D., an NIH distinguished investigator, head of NHGRI’s Inflammatory Disease Section and a senior author of the paper.

    “We hope to continue studying other molecules in this pathway and how they are altered in patients with disabling pansclerotic morphea and related conditions to find clues to understanding a broader array of more common diseases,” said Lori Broderick, M.D., Ph.D., a senior author of the paper and an associate professor at UCSD.

    Reference: “Variant STAT4 and Response to Ruxolitinib in an Autoinflammatory Syndrome” by Hratch Baghdassarian, B.S., Sarah A. Blackstone, B.S., Owen S. Clay, M.D., Ph.D., Rachael Philips, Ph.D., Brynja Matthiasardottir, M.Sc., Michele Nehrebecky, N.P., Vivian K. Hua, B.S., Rachael McVicar, B.S., Yang Liu, Ph.D., Suzanne M. Tucker, M.D., Davide Randazzo, Ph.D., Natalie Deuitch, M.S., Sofia Rosenzweig, B.S., Adam Mark, M.S., Roman Sasik, Ph.D., Kathleen M. Fisch, Ph.D., Pallavi Pimpale Chavan, M.D., Elif Eren, Ph.D., Norman R. Watts, Ph.D., Chi A. Ma, Ph.D., Massimo Gadina, Ph.D., Daniella M. Schwartz, M.D., Anwesha Sanyal, Ph.D., Giffin Werner, B.S., David R. Murdock, M.D., Nobuyuki Horita, M.D., Ph.D., Shimul Chowdhury, Ph.D., David Dimmock, M.D., Kristen Jepsen, Ph.D., Elaine F. Remmers, Ph.D., Raphaela Goldbach-Mansky, M.D., M.H.S., William A. Gahl, M.D., Ph.D., John J. O’Shea, M.D., Joshua D. Milner, M.D., Nathan E. Lewis, Ph.D., Johanna Chang, M.D., Daniel L. Kastner, M.D., Ph.D., Kathryn Torok, M.D., Hirotsugu Oda, M.D., Ph.D., Christopher D. Putnam, Ph.D. and Lori Broderick, M.D., Ph.D., 31 May 2023, New England Journal of Medicine.
    DOI: 10.1056/NEJMoa2202318

    University of Louisville researchers receive $5.8 million to prevent immune system dysregulation

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    Researchers at the University of Louisville have received $5.8 million in two grants from the National Institutes of Health to expand their work to better understand and prevent immune system dysregulation responsible for acute respiratory distress, the condition responsible for serious illness and death in some COVID-19 patients. A separate $306,000 NIH Small Business Innovation Research grant supports early testing of a compound developed at UofL as a potential treatment.

    The three grants combined total $6.1 million.

    During the pandemic, health care providers worked tirelessly to treat patients who became seriously ill with COVID-19. Some of those patients developed severe lung disease known as acute respiratory distress syndrome (ARDS) due to an excessive response of the immune system often called cytokine storm.

    As they treated these critically ill patients, physicians and other providers at UofL Health shared their clinical insights and patient samples with researchers at UofL to discover the cause of the immune system overresponse.

    At one time we had over 100 patients with COVID in the hospital. Once they were on a ventilator, mortality was about 50%. We were looking at this issue to see why some people would do well while some developed bad lung disease and did not do well or died.”

    Jiapeng Huang, an anesthesiologist with UofL Health and professor and vice chair of the Department of Anesthesiology and Perioperative Medicine in the UofL School of Medicine

    The UofL researchers, led by immunologist Jun Yan, discovered that a specific type of immune cells, low-density inflammatory neutrophils, became highly elevated in some COVID-19 patients whose condition became very severe. This elevation signaled a clinical crisis point and increased likelihood of death within a few days due to lung inflammation, blood clotting and stroke. Their findings were published in 2021 in JCI Insight.

    With the new NIH funding, Yan is leading research to build on this discovery with deeper understanding of what causes a patient’s immune system to respond to an infection in this way and develop methods to predict, prevent or control the response.

    “Through this fruitful collaboration, we now have acquired NIH funding for basic and translational studies and even progress toward commercialization of a potential therapy,” Yan said. “That’s why we do this research – eventually we want to benefit the patients.”

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    Yan, chief of the UofL Division of Immunotherapy in the Department of Surgery, a professor of microbiology and immunology and a senior member of the Brown Cancer Center, will lead the new research, along with Huang and Silvia M. Uriarte, university scholar and professor in the Department of Oral Immunology and Infectious Diseases in the UofL School of Dentistry.

    “COVID-19 continues to spotlight the impactful synergy between the clinical and research teams at the University of Louisville,” said Jason Smith, UofL Health chief medical officer. “Innovation is in the DNA of academic medicine. We collaborate to provide each patient the best options for prevention and treatment today, while developing the even better options for tomorrow.”

    In addition to two research grants of $2.9 million each awarded directly to UofL, a $306,000 grant to a startup company will support early testing of a compound developed in the lab of UofL Professor of Medicine Kenneth McLeish that shows promise in preventing the dangerous cytokine storm while allowing the neutrophils to retain their ability to kill harmful bacteria and viruses. The compound, DGN-23, will be tested by UofL and Degranin Therapeutics, a startup operated by McLeish, Yan, Huang, Uriarte and Madhavi Rane, associate professor in the Department of Medicine.

    “This is one more example of how UofL has led the charge in finding new and innovative ways to detect, contain and fight COVID-19 and other potential public health threats,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “This team’s new research and technology could help keep people healthy and safe here and beyond.”

    The knowledge gained through these studies may benefit not only COVID-19 patients, but those with other conditions in which immune dysregulation can occur, such as other types of viral and bacterial pneumonia and autoimmune diseases, and patients undergoing cancer immunotherapy and organ transplantation.

    The grants

    Grant 1 – $2.9 million, four-year grant to UofL. Investigators will study the new subset of neutrophils Yan identified to better understand how they contribute to acute respiratory distress and clotting. They also will determine whether a novel compound will prevent these complications. They will use lab techniques and studies with animal models that allow for manipulation of certain conditions that cannot be done in human subjects.

    Grant 2 – $2.9 million, five-year grant to UofL. This work examines a more comprehensive landscape to characterize different subsets of neutrophils and measure their changes over the course of COVID-19 disease progression and how neutrophils contribute to immune dysfunction.

    Grant 3 – $306,000, one-year grant to Degranin Therapeutics and UofL for early testing of DGN-23, a compound developed at UofL, to determine its effectiveness in preventing or reducing immune dysregulation.

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    Gaming bacterial metabolism

    Valeri, J.A., Krishnan, A. & Collins, J.J. Gaming bacterial metabolism.
    Nat Microbiol 8, 1004–1005 (2023). https://doi.org/10.1038/s41564-023-01390-2

    The Future of Food Safety: Detecting Pathogens Before They Cause Illness

    Common food items like lettuce and spinach are regularly subjected to testing for harmful bacteria such as salmonella, listeria monocytogenes, and dangerous strains of E. coli as a means of preventing consumer illness.

    Despite the availability of quick testing methods, it’s still a time-consuming process to determine who fell ill and trace the source of the tainted produce. That’s far too late for the many Americans who already ate the produce. The current solution, frequently involving a recall spanning multiple states, essentially amounts to damage control.

    The University of Delaware researchers want to spot these bacteria before anyone ever falls ill. As detailed in an article published in the Journal of Food Safety, UD and Delaware-based startup Biospection are about to speed up testing — a lot. Faculty members Harsh Bais and Kali Kniel, alongside former graduate student Nick Johnson, teamed up with Andy Ragone of Biospection to detect foodborne pathogens in three to six hours.

    A microbiologist by trade, Kniel is an expert on crossover pathogens like salmonella, which gleefully jump to new hosts like that delicious, fresh lettuce.

    “While the produce industry is working diligently to reduce risks associated with microbial contamination, tools like this have incredible potential to improve risk reduction strategies,” said Kniel, professor of microbial food safety who works regularly with industry and government agencies to reduce risk of foodborne illness. “Collaborations like ours between academics and biotechnology companies can enhance technology and impact food safety and public health.”

    These pathogens easily find their way into plants, which are unfortunately very welcoming hosts — hosts that can’t tell you where their guests are.

    Just like humans, plants use defense mechanisms to fight disease. But some human-borne pathogens learned to push open a plant’s open-entry gates called stomates — pores in the leaves or stem — and make themselves at home.

    “Because these bacteria are not true pathogens for plants, you cannot physically see early signs that the plant is under stress,” said Bais, UD professor of plant biology. “Biospection’s technology allows us to say, very quickly, if the opportunistic human pathogen is present in the plant.”

    As a chemical physicist working in Wilmington, Ragone got to know Kniel and Bais through Delaware’s scientific community and lab equipment sharing. A relationship built over time, culminating when Kniel, Bais, and Ragone applied for and received research funding from a Delaware Biotechnology Institute Center for Advanced Technology (CAT) grant for scientific technology and intellectual property.

    The researchers married their interdisciplinary expertise to reduce the risk of foodborne illness, a task that industry and academic researchers struggled with for many years. The result? The team created a multi-spectral imaging platform to look at plant sentinel response. A goal is to use this technique directly on a conveyor, scanning your lettuce before it ever heads to the grocery store.

    So how do you see a symptom that you can’t see? The researchers’ technique scans leaves via multispectral imaging and deep UV sensing when the plant is attracting these pathogens. When the researchers looked at benign bacteria, they observed little change. But, with harmful, human-borne pathogens, the test can spot differences in the plant under attack.

    “Using listeria as an example, in three to six hours, we see a sharp drop of chlorophyll pigments,” Bais said. “That’s a strong signal that the plant is responding physiologically — a marker of unusual bacteria.”

    The new, multi-spectral imaging technique is non-invasive, and lightning-fast compared to current tests, where a lab scientist extracts a leaf, grinds it up, plates the bacteria, and looks for disease. The current method is not commercially available, but Biospection was awarded a National Science Foundation Small Business Innovation Research grant in 2022 to develop and commercialize it into a real-time imaging sensor to inspect plants for disease and other stresses.

    “Harsh and Kali were certainly instrumental in the techniques that we developed with multi-spectral imaging and the use of deep ultraviolet fluorescence,” said Ragone, founder and chief technology officer of Biospection. “We built a portable instrument that could be commercialized.”

    Vertical farming is an agricultural sector that stands to reap the benefits of this new technology. Using less water and less space, vertical farms are a vital step towards more sustainable agriculture. But when it comes to disease, these farms are just as vulnerable as traditional, outdoor agriculture. An incidence of E. coli means a vertical farm must throw away an entire harvest.

    Biospection is already working with agricultural companies to embed the imaging sensor into vertical farms’ shelves and, for outdoor farms, crop drones.

    “Working with UD, we’ve laid the scientific foundation to create better instruments,” Ragone said. “We’re working toward an instrument that’s portable, automated, and can give an answer in a matter of seconds.”

    For future research, Bais has his eye on determining if this technology can differentiate between different microbes.

    “If the sentinel response is different from one microbe to the other, that gives us the identity of the microbe based on plant sentinel response. We haven’t gone there yet, but that would be the ultimate achievement,” Bais said. “In one sentinel, then you could differentiate between what benign and harmful microbes does this in terms of one sentinel.”

    Reference: “Deep ultraviolet fluorescence sensing with multispectral imaging to detect and monitor food-borne pathogens on the leafy green phyllosphere” by Nick Johnson, Kalmia Kniel, Harsh Bais and Anthony Ragone, 16 April 2023, Journal of Food Safety.
    DOI: 10.1111/jfs.13056

    Experts find remnants of ancient RNA viruses embedded inside reef-building corals

    An international team of marine biologists has discovered the remnants of ancient RNA viruses embedded in the DNA of symbiotic organisms living inside reef-building corals.

    The RNA fragments are from viruses that infected the symbionts as long ago as 160 million years. The discovery is described in an open-access study published this week in the Nature journal Communications Biology, and it could help scientists understand how corals and their partners fight off viral infections today. But it was a surprising find because most RNA viruses are not known for embedding themselves in the DNA of organisms they infect.

    The research showed that endogenous viral elements, or EVEs, appear widely in the genomes of coral symbionts. Known as dinoflagellates, the single-celled algae live inside corals and provide them with their dramatic colors. The EVE discovery underscores recent observations that viruses other than retroviruses can integrate fragments of their genetic code into their hosts’ genomes.

    So why did it get in there? It could just be an accident, but people are starting to find that these ‘accidents’ are more frequent than scientists had previously believed, and they’ve been found across all kinds of hosts, from bats to ants to plants to algae.”

    Adrienne Correa, Study Co-Author, Rice University

    That an RNA virus appears at all in coral symbionts was also a surprise.

    “This is what made this project so interesting to me,” said study lead author Alex Veglia, a graduate student in Correa’s research group. “There’s really no reason, based on what we know, for this virus to be in the symbionts’ genome.”

    The study was supported by the Tara Ocean Foundation and the National Science Foundation and led by Correa, Veglia and two scientists from Oregon State University, postdoctoral scholar Kalia Bistolas and marine ecologist Rebecca Vega Thurber. The research provides clues that can help scientists better understand the ecological and economic impact of viruses on reef health.

    The researchers did not find EVEs from RNA viruses in samples of filtered seawater or in the genomes of dinoflagellate-free stony corals, hydrocorals or jellyfish. But EVEs were pervasive in coral symbionts that were collected from dozens of coral reef sites, meaning the pathogenic viruses were -; and probably remain -; picky about their target hosts.

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    “There’s a huge diversity of viruses on the planet,” said Correa, an assistant professor of biosciences. “Some we know a lot about, but most viruses haven’t been characterized. We might be able to detect them, but we don’t know who serves as their hosts.”

    She said viruses, including retroviruses, have many ways to replicate by infecting hosts. “One reason our study is cool is because this RNA virus is not a retrovirus,” Correa said. “Given that, you wouldn’t expect it to integrate into host DNA.

    “For quite a few years, we’ve seen a ton of viruses in coral colonies, but it’s been hard to tell for sure what they were infecting,” Correa said. “So this is likely the best, most concrete information we have for the actual host of a coral colony-associated virus. Now we can start asking why the symbiont keeps that DNA, or part of the genome. Why wasn’t it lost a long time ago?”

    The discovery that the EVEs have been conserved for millions of years suggests they may somehow be beneficial to the coral symbionts and that there is some kind of mechanism that drives the genomic integration of the EVEs.

    “There are a lot of avenues we can pursue next, like whether these elements are being used for antiviral mechanisms within dinoflagellates, and how they are likely to affect reef health, especially as oceans warm,” Veglia said.

    “If we’re dealing with an increase in the temperature of seawater, is it more likely that Symbiodiniaceae species will contain this endogenous viral element? Does having EVEs in their genomes improve their odds of fighting off infections from contemporary RNA viruses?” he said.

    “In another paper, we showed there was an increase in RNA viral infections when corals underwent thermal stress. So there are a lot of moving parts. And this is another good piece of that puzzle.”

    Correa said, “We can’t assume that this virus has a negative effect. But at the same time, it does look like it’s becoming more productive under these temperature stress conditions.”

    Thurber is the Emile F. Pernot Distinguished Professor in Oregon State’s Department of Microbiology.

    Source:
    Journal reference:

    Veglia, A. J., et al. (2023). Endogenous viral elements reveal associations between a non-retroviral RNA virus and symbiotic dinoflagellate genomes. Communications Biology. doi.org/10.1038/s42003-023-04917-9.

    Why do some people live to be 100? Intestinal bacteria may hold the answer

    We are pursuing the dream of eternal life. We fast to stay healthy. And each year, we spend billions of kroner on treatment to make sure we stay alive. But some people turn 100 years old all by themselves. Why is that?

    Researchers from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen have set out to find the answer.

    Studying 176 healthy Japanese centenarians, the researchers learned that the combination of intestinal bacteria and bacterial viruses of these people is quite unique.

    “We are always eager to find out why some people live extremely long lives. Previous research has shown that the intestinal bacteria of old Japanese citizens produce brand new molecules that make them resistant to pathogenic — that is, disease-promoting — microorganisms. And if their intestines are better protected against infection, well, then that is probably one of the things that cause them to live longer than others,” says Postdoc Joachim Johansen, who is first author of the new study.

    Among other things, the new study shows that specific viruses in the intestines can have a beneficial effect on the intestinal flora and thus on our health.

    “Our intestines contain billions of viruses living of and inside bacteria, and they could not care less about human cells; instead, they infect the bacterial cells. And seeing as there are hundreds of different types of bacteria in our intestines, there are also lots of bacterial viruses,” says Associate Professor Simon Rasmussen, last author of the new study.

    Joachim Johansen adds that aside from the important, new, protective bacterial viruses, the researchers also found that the intestinal flora of the Japanese centenarians is extremely interesting.

    “We found great biological diversity in both bacteria and bacterial viruses in the centenarians. High microbial diversity is usually associated with a healthy gut microbiome. And we expect people with a healthy gut microbiome to be better protected against aging related diseases,” says Joachim Johansen.

    Once we know what the intestinal flora of centenarians looks like, we can get closer to understanding how we can increase the life expectancy of other people. Using an algorithm designed by the researchers, they managed to map the intestinal bacteria and bacterial viruses of the centenarians.

    “We want to understand the dynamics of the intestinal flora. How do the different kinds of bacteria and viruses interact? How can we engineer a microbiome that can help us live healthy, long lives? Are some bacteria better than others? Using the algorithm, we are able to describe the balance between viruses and bacteria,” says Simon Rasmussen.

    And if the researchers are able to understand the connection between viruses and bacteria in the Japanese centenarians, they may be able to tell what the optimal balance of viruses and bacteria looks like.

    Optimising intestinal bacteria

    More specifically, the new knowledge on intestinal bacteria may help us understand how we should optimise the bacteria found in the human body to protect it against disease.

    “We have learned that if a virus pays a bacterium a visit, it may actually strengthen the bacterium. The viruses we found in the healthy Japanese centenarians contained extra genes that could boost the bacteria. We learned that they were able to boost the transformation of specific molecules in the intestines, which might serve to stabilise the intestinal flora and counteract inflammation,” says Joachim Johansen, and Simon Rasmussen adds:

    “If you discover bacteria and viruses that have a positive effect on the human intestinal flora, the obvious next step is to find out whether only some or all of us have them. If we are able to get these bacteria and their viruses to move in with the people who do not have them, more people could benefit from them.”

    Even though this requires more research, the new insight is significant, because we are able to modify the intestinal flora.

    “Intestinal bacteria are a natural part of the human body and of our natural environment. And the crazy thing is that we can actually change the composition of intestinal bacteria. We cannot change the genes — at least not for a long time to come. If we know why viruses and intestinal bacteria are a good match, it will be a lot easier for us to change something that actually affects our health,” says Simon Rasmussen.

  • Joachim Johansen, Koji Atarashi, Yasumichi Arai, Nobuyoshi Hirose, Søren J. Sørensen, Tommi Vatanen, Mikael Knip, Kenya Honda, Ramnik J. Xavier, Simon Rasmussen, Damian R. Plichta. Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan. Nature Microbiology, 2023; DOI: 10.1038/s41564-023-01370-6
  • University of Copenhagen – The Faculty of Health and Medical Sciences

    Does COVID-19 Vaccination Cause Changes to Women’s Periods?

    A recent study has concluded that there is no cause for alarm regarding changes to menstrual cycles due to the Covid-19 vaccination.

    However, the study points out that women who have contracted the Covid-19 virus may experience an increased likelihood of disruptions in their menstrual cycle. These disruptions could manifest as skipped or heavier menstrual periods, or even bleeding between periods.

    The research provides reassurance to women who might have avoided vaccination because they were concerned about the impact on their periods, the study says.

    Researchers from the Universities of Edinburgh, Montpellier, Oxford, Bristol, and Exeter investigated results from a survey conducted in the UK in March 2021.

    Participants were asked about any menstrual changes during the pandemic, their Covid-19 vaccination history, and whether they had ever had Covid-19.

    The researchers examined results from almost 5,000 pre-menopausal participants who had been vaccinated against Covid-19.

    The vast majority – 82 percent – reported no menstrual changes. Only 6.2 percent reported more disruption, 1.6 percent reported less disruption, and 10.2 percent reported ‘other changes’, which could refer to things like changes to cycle length and regularity, or amount of menstrual bleeding.

    Of the 18 percent who reported changes, the risk was higher among those who smoked, previously had Covid-19, or who were not using oestradiol-containing contraceptives such as the combined contraceptive pill.

    The researchers then looked at a wider group of 12,000 participants, including those who were vaccinated and unvaccinated against Covid-19.

    Compared to those who were not vaccinated, and had never had Covid-19, vaccination alone did not show increased abnormal menstrual cycle factors. Those who had a history of Covid-19, however, were at increased risk of reporting heavier bleeding, missed periods, and bleeding between periods.

    The study was carried out against a background of public concern that the Covid-19 pandemic had caused disruption to menstrual cycles due to vaccination, infection with the virus, and lifestyle changes.

    There has been a lack of research into how much each factor has contributed to the changes and who is most at risk, but this research provides valuable information about the understudied area of periods and Covid-19, experts say.

    The team hopes that the results will help healthcare professionals when counseling women about the relative risks of menstrual disturbance when getting vaccinated against Covid-19, compared with having the infection itself, and also help women make decisions about Covid-19 vaccination.

    The findings have been published in the journal iScience.

    Dr. Jackie Maybin, a principal investigator in the University of Edinburgh’s MRC Centre for Reproductive Health, and one of the study authors, said: “These results rely on people recalling their previous menstrual experiences, and may include bias due to those who chose to complete the survey. Nevertheless, our results are reassuring that Covid-19 vaccination does not cause concerning menstrual changes, and helpful for identifying people who might be at higher risk of experiencing menstrual disturbance.”

    Reference: “A retrospective case-control study on menstrual cycle changes following COVID-19 vaccination and disease” by Alexandra Alvergne, Gabriella Kountourides, M. Austin Argentieri, Lisa Agyen, Natalie Rogers, Dawn Knight, Gemma C. Sharp, Jacqueline A. Maybin, and Zuzanna Olszewska, 15 March 2023, iScience.
    DOI: 10.1016/j.isci.2023.106401

    Top 10 most downloaded papers: Access Microbiology

    Top 10 most downloaded papers: Access Microbiology

    Posted on June 1, 2023   by Microbiology Society


    Publishing in Access Microbiology – our sound science open research platform – is free until the end of June 2023. Submit your manuscript before the end of the month to make the most of free Open Access publication.

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    Access Microbiology publishes a range of sound science research, including replication studies, negative or null results, research proposals, case reports and more. We welcome work from all branches of microbiology and virology, offering fully transparent peer review.

    See the top 10 most downloaded papers from 2019 to May 2023 below:

    When good bacteria behave badly: a case report of Bacillus clausii sepsis in an immunocompetant adult

    Isabella Princess, T. Natarajan, Siddhartha Ghosh​

    Case Report

    9350 full text downloads

    A case report: insights into reducing plastic waste in a microbiology laboratory    

    Joana Alves, Fiona A. Sargison, Hanne Stawarz, Willow B. Fox, Samuel G. Huete, Amany Hassan,​ Brian McTeir, Amy C. Pickering

    Short Communication

    9017 full text downloads

    High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

    María Eugenia Soria, Marta Cortón, Brenda Martínez-González, Rebeca Lobo-Vega, Lucía Vázquez-Sirvent, Rosario López-Rodríguez​, Berta Almoguera​, Ignacio Mahillo​, Pablo Mínguez, Antonio Herrero, Juan Carlos Taracido​, Alicia Macías-Valcayo, Jaime Esteban, Ricardo Fernandez-Roblas​, Ignacio Gadea, Javier Ruíz-Hornillos​, Carmen Ayuso, Celia Perales

    Short Communication

    8714 full text downloads

    Disseminated sporotrichosis in a person with human immunodeficiency virus disease

    Vhudzani Tshisevhe, Lebogang Skosana, Kagiso Motse, Tinashe Maphosa, Barend Mitton​

    Case Report

    8225 full text downloads

    Phylogenetic diversity and activity screening of cultivable Actinobacteria isolated from marine sponges and associated environments from the western coast of India

    Ulfat Baig​, Neelesh Dahanukar, Neha Shintre, Ketki Holkar​, Anagha Pund​, Uttara Lele​, Tejal Gujarathi​, Kajal Patel​, Avantika Jakati​, Ruby Singh​, Harshada Vidwans​, Vaijayanti Tamhane, Neelima Deshpande​, Milind Watve

    Research Article

    8223 full text downloads

    Not all wavelengths are created equal: disinfection of SARS-CoV-2 using UVC radiation is wavelength-dependent

    Richard M. Mariita, James W. Peterson

    Short Communication

    8214 full text downloads

    Streptococcus lutetiensis neonatal meningitis with empyema

    Allen T. Yu, Kate Shapiro​, Christy A. Beneri, Lisa S. Wilks-Gallo

    Case Report

    8173 full text downloads

    Disinfection of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and Acinetobacter baumannii using Klaran WD array system

    Richard M. Mariita, Rajul V. Randive

    Short Communication

    8106 full text downloads

    Distribution of cycle threshold values in RT-qPCR tests during the autumn 2020 peak of the COVID-19 pandemic in the Czech Republic

    Michal Koblížek, Daniela Hávová​, Karel Kopejtka, Jürgen Tomasch, Kateřina Bišová

    Short Communication

    8000 full text downloads

    Rapid growth atypical mycobacteria infection associated with growth hormone injections: a case report

    Christian David Cardozo Lomaquiz, Tamara Frontanilla, Natalia Scavone, Alba Fretes​, Nathalia Torales, María Elena Pereira​, Herminia Mino de Kaspar, Xavier Ortiz​, Renate Henning

    Case Report

    7992 full text downloads


    Download data from 23rd May 2023

    Microbiome: From Research and Innovation to Market