Tag Archives: Biology

Designing more useful bacteria

In a step forward for genetic engineering and synthetic biology, researchers have modified a strain of Escherichia coli bacteria to be immune to natural viral infections while also minimizing the potential for the bacteria or their modified genes to escape into the wild.

The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels. Currently, viruses that infect vats of bacteria can halt production, compromise drug safety, and cost millions of dollars.

Results are published March 15 in Nature.

“We believe we have developed the first technology to design an organism that can’t be infected by any known virus,” said the study’s first author, Akos Nyerges, research fellow in genetics in the lab of George Church in the Blavatnik Institute at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering.

“We can’t say it’s fully virus-resistant, but so far, based on extensive laboratory experiments and computational analysis, we haven’t found a virus that can break it,” Nyerges said.

The work also provides the first built-in safety measure that prevents modified genetic material from being incorporated into natural cells, he said.

The authors said their work suggests a general method for making any organism immune to viruses and preventing gene flow into and out of genetically modified organisms (GMOs). Such biocontainment strategies are of increasing interest as groups explore the safe deployment of GMOs for growing crops, reducing disease spread, generating biofuels, and removing pollutants from open environments.

Building on what came before

The findings build on earlier efforts by genetic engineers to achieve a helpful, safe, virus-resistant bacterium.

In 2022, a group from the University of Cambridge thought they’d made an E. coli strain immune to viruses. But then Nyerges teamed up with research fellow Siân Owen and graduate student Eleanor Rand in the lab of co-author Michael Baym, assistant professor of biomedical informatics in the Blavatnik Institute at HMS. When they sampled local sites rife with E. coli, including chicken sheds, rat nests, sewage, and the Muddy River down the street from the HMS campus, they discovered viruses that could still infect the modified bacteria.

Discovering that the bacteria weren’t fully virus-resistant “was a bummer,” Nyerges said.

The initial method had involved genetically reprogramming E. coli to make all their life-sustaining proteins from 61 sets of genetic building blocks, or codons, instead of the naturally occurring 64. The idea was that viruses wouldn’t be able to hijack the cells because they couldn’t replicate without the missing codons.

The HMS team, however, figured out that deleting codons wasn’t enough. Some viruses were bringing in their own equipment to get around the missing pieces.

So, Nyerges and colleagues developed a way to change what those codons tell an organism to make — something scientists hadn’t done to this extent in living cells.

Lost in translation

The key lay in transfer RNAs, or tRNAs.

Each tRNA’s role is to recognize a specific codon and add the corresponding amino acid to a protein that’s being built. For instance, the codon TCG tells its matching tRNA to attach the amino acid serine.

In this case, the Cambridge team had deleted TCG along with sister codon TCA, which also calls for serine. The team had also removed the corresponding tRNAs.

The HMS team now added new, trickster tRNAs in their place. When these tRNAs see TCG or TCA, they add leucine instead of serine.

“Leucine is about as different from serine as you can get, physically and chemically,” said Nyerges.

When an invading virus injects its own genetic code full of TCG and TCA and tries to tell the E. coli to make viral proteins, these tRNAs mess up the virus’s instructions.

Inserting the wrong amino acids results in misfolded, nonfunctional viral proteins. That means the virus can’t replicate and go on to infect more cells.

Viruses, however, also come equipped with their own tRNAs. These can still accurately turn TCG and TCA into serine. But Nyerges and colleagues provided evidence that the trickster tRNAs they introduced are so good at their jobs that they overpower their viral counterparts.

“It was very challenging and a big achievement to demonstrate that it’s possible to swap an organism’s genetic code,” said Nyerges, “and that it only works if we do it this way.”

The work may have cleared the last hurdle in rendering a bacterium immune to all viruses, although there’s still a chance something will appear that can break the protection, the authors said.

The team takes confidence in knowing that overcoming the swapped codons would require a virus to develop dozens of specific mutations at the same time.

“That’s very, very unlikely for natural evolution,” Nyerges said.

Safety measures

The work incorporates two separate safeguards.

The first protects against horizontal gene transfer, a constantly occurring phenomenon in which snippets of genetic code and their accompanying traits, such as antibiotic resistance, get transferred from one organism to another.

Nyerges and colleagues short-circuited this outcome by making substitutions throughout genes in the modified E. coli cells so that all codons that call for leucine got replaced with TCG or TCA — the codons that in an unmodified organism would call for serine. The bacteria still correctly made leucine in those places because of their trickster tRNAs.

If another organism were to incorporate any of the modified snippets into its own genome, though, the organism’s natural tRNAs would interpret TCG and TCA as serine and end up with junk proteins that don’t convey any evolutionary advantage.

“The genetic information will be gibberish,” said Nyerges.

Similarly, the team showed that if one of the E. coli‘s trickster tRNAs gets transferred to another organism, its misreading of serine codons as leucine codons damages or kills the cell, preventing further spread.

“Any modified tRNAs that escape won’t get far because they are toxic to natural organisms,” said Nyerges.

The work represents the first technology that prevents horizontal gene transfer from genetically modified organisms into natural organisms, he said.

For the second fail-safe, the team designed the bacteria themselves to be unable to live outside a controlled environment.

The team used an existing technology developed by the Church lab to make the E. coli reliant on a lab-made amino acid that doesn’t exist in the wild. Workers cultivating these E. coli to produce insulin, for instance, would feed them the unnatural amino acid. But if any bacteria escaped, they would lose access to that amino acid and die.

Therefore, no humans or other creatures are at risk of getting infected by “superbacteria,” Nyerges emphasized.

Nyerges looks forward to exploring codon reprogramming as a tool for coaxing bacteria to produce medically useful synthetic materials that would otherwise require expensive chemistry. Other doors have yet to be opened.

“Who knows what else?” he mused. “We’ve just started exploring.”

  • Akos Nyerges, Svenja Vinke, Regan Flynn, Siân V. Owen, Eleanor A. Rand, Bogdan Budnik, Eric Keen, Kamesh Narasimhan, Jorge A. Marchand, Maximilien Baas-Thomas, Min Liu, Kangming Chen, Anush Chiappino-Pepe, Fangxiang Hu, Michael Baym, George M. Church. A swapped genetic code prevents viral infections and gene transfer. Nature, 2023; DOI: 10.1038/s41586-023-05824-z
  • Harvard Medical School

    Antibiotics can destroy many types of bacteria, but increasingly, bacterial pathogens are gaining resistance to many commonly used …

    Antibiotics can destroy many types of bacteria, but increasingly, bacterial pathogens are gaining resistance to many commonly used types. As the threat of antibiotic resistance looms large, researchers have sought to find new antibiotics and other ways to destroy dangerous bacteria. But new antibiotics can be extremely difficult to identify and test. Bacteriophages, which are viruses that only infect bacterial cells, might offer an alternative. Bacteriophages (phages) were studied many years ago, before the development of antibiotic drugs, and they could help us once again.

    Image credit: Pixabay

    If we are going to use bacteriophages in the clinic to treat humans, we should understand how they work, and how bacteria can also become resistant to them. Microbes are in an arms race with each other, so while phages can infect bacteria, some bacterial cells have found ways to thwart the effects of those phages. New research reported in Nature Microbiology has shown that when certain bacteria carry a specific genetic mutation, phages don’t work against them anymore.

    In this study, the researchers used a new technique so they could actually see a phage attacking bacteria. Mycobacteriophages infect Mycobacterial species, including the pathogens Mycobacterium tuberculosis and Mycobacterium abscessus, as well as the harmless Mycobacterium smegmatis, which was used in this research.

    The scientists determined that Mycobacterial gene called lsr2 is essential for many mycobacteriophages to successfully infect Mycobacteria. Mycobacteria that carry a mutation that renders the Lsr2 protein non-functional are resistant to these phages.

    Normally, Lsr2 aids in DNA replication in bacterial cells. Bacteriophages can harness this protein, however, and use it to reproduce the phage’s DNA. Thus, when Lsr2 stops working, the phage cannot replicate and it cannot manipulate bacterial cells.

    In the video above, by first study author Charles Dulberger, a genetically engineered mutant phage infects Mycobacterium smegmatis. First, one phage particle (red dot at 0.42 seconds) binds to a bacterium. The phage DNA (green fluorescence) is injected into the bacterial cell (2-second mark). The bright green dots at the cells’ ends are not relevant. For a few seconds, the DNA forms a zone of phage replication, and fills the cell. Finally, the cell explodes at 6:25 seconds. (About three hours have been compressed to make this video.)

    The approach used in this study can also be used to investigate other links between bacteriophages and the bacteria they infect.

    “This paper focuses on just one bacterial protein,” noted co-corresponding study author Graham Hatfull, a Professor at the University of Pittsburgh. But there are many more opportunities to use this technique. “There are lots of different phages and lots of other proteins.”

    Sources: University of Pittsburgh, Nature Microbiology

    Carmen Leitch

    In recent years, we have learned a lot about the crucial role gut microbes play in our health …

    In recent years, we have learned a lot about the crucial role gut microbes play in our health and well being. The extent of their influence can be surprising at times. Research has shown that gut microbes can impact the repair of tissue damage by fueling the production of a type of immune cell called Tregs, or regulatory T cells. These cells reside in various tissues and help regulate inflammation and immunity in different organs. But new work has shown that Tregs can also move around the body and respond when they are called to help fix injuries and tissue damage, such as in the muscles and liver. The findings, which used a mouse model and still have to be confirmed in humans, have been reported in the journal Immunity.

    Image credit: Pixabay

    There are Tregs that reside in the colon, and these cells are known to play an important role in the maintenance of gut health. The immune system in the gut has to protect us from infection while also ignoring the harmless or beneficial microbes in the gut microbiome. Gut microbes have also been known to affect Treg production. But colonic Tregs were thought to stay in the gut. In this study, the investigators found colonic Tregs among muscle cells.

    First study author Bola Hanna, a research fellow in immunology at Harvard Medical School (HMS) noticed cells that looked like gut-derived Tregs among muscle tissue. The researchers wanted to known more about these mysterious cells. First, they confirmed the identity of the Tregs by analyzing gene expression and molecular characteristics. This indicated that these cells were just like colonic Tregs. Next, the investigators tagged those cells and watched as they moved around the bodies of a mouse model. The researchers assessed the antigens on these cells as well, confirming that they were equivalent to Tregs from the gut.

    When a mouse model was created to lack these Tregs, and was then subjected to muscle injury, the mice had high levels of inflammation and difficulty healing. When healing did happen, it was accompanied by scarring.

    In another experiment, mice were given antibiotics to reduce the levels of gut microbes. Once again, when muscle injury occurred, it took longer to heal. But if the gut microbiome was restored, normal healing commenced.

    The colonic Tregs are promoting healing in muscles by reducing the levels of an inflammatory molecule called IL-17.

    The investigators also found evidence of gut Tregs in different organs including the kidneys, liver, and spleen. In a mouse model of fatty liver disease, there were unusually high levels of colonic Tregs compared to healthy mice, suggesting that Tregs are influencing inflammation in a variety of tissues.

    In the mouse model of fatty liver disease, symptoms got worse when the mice lacked Tregs, which also seems to confirm that colonic Tregs are playing an important role in countering the effects of inflammation due to fatty liver disease.

    “Our observations indicate that gut microbes drive the production of a class of regulatory T cells that are constantly exiting the gut and act as sentries that sense damage at distant sites in the body and then act as emissaries to repair that damage,” explained senior study author Diane Mathis, a professor of immunology in the Blavatnik Institute at HMS. This work may also help scientists create therapies for fatty liver disease.

    Sources: Harvard Medical School, Immunity

    Carmen Leitch

    Adult T-cell leukemia/lymphoma (ATLL) is a rare type of cancer that impacts T cells, a crucial immune cell …

    Adult T-cell leukemia/lymphoma (ATLL) is a rare type of cancer that impacts T cells, a crucial immune cell that plays an important role in fighting infection. ATLL tends to be aggressive, and can manifest in the blood as leukemia, in the lymph nodes as lymphoma, or other tissues like the skin. ATLL has been associated with human T-cell lymphotropic virus type 1 (HTLV-1) infections, although fewer than five percent of people with this virus end up developing ATLL. Right now, clinicians cannot predict which people with HTLV-1 infections will get ATLL. While some types of ATLL tumors can be surgically removed, survival prospects for these patients is not good.

    Image credit: Pixabay

    A recent article published in Genes & Cancer noted that even though a monoclonal antibody that can treat ATLL called mogamulizumab has recently been approved, the survival rate is still poor.

    Viruses are known to change gene expression in host cells, and HTLV-1 is no different. Previous work reported in PLOS Pathogens showed that when HTLV-1 infects cells, it causes a huge number of genetic and epigenetic changes with viral proteins it generates called Tax and HBZ. These many genetic changes could be interfering with chemotherapeutics and may render them less effective, suggested researcher Tatsuro Jo of the Nagasaki Genbaku Hospital.

    In the HTLV-1 genome, there is an opportunity, however. Its genome is completely different from the human genome, so the viral proteins generated during HTLV-1 infection are excellent therapeutic targets. ATLL survivors have been found to carry cytotoxic T lymphocytes that work against the HTLV-1 Tax protein. People who survive ATLL over the long term may have been able to activate strong antitumor mechanisms.

    Jo added that some people who have lived for a long time after an ATLL diagnosis, and prior to the approval of mogamulizumab, had also developed herpesvirus infections. It’s been suggested that herpes infections can trigger powerful cellular immunity mechanisms.

    “Although contracting herpes simplex or herpes zoster is unpleasant, the mechanism by which these herpesvirus infections can produce a therapeutic effect on refractory ATLL via the activation of the host’s cellular immunity is extremely interesting and worth further study,” said Jo.

    Sources: Impact Journals LLC, Genes & Cancer

    Carmen Leitch

    Long COVID still affects many people who had a case of COVID-19; even people who had mild cases …

    Long COVID still affects many people who had a case of COVID-19; even people who had mild cases and were not hospitalized are at risk for the chronic disorder. Scientists and clinicians are still learning about the illness, which causes a wide range of symptoms and happens for unknown reasons. There are several hypotheses, however, and the disorder may also arise in different people for different reasons. New research has suggested that long COVID happens because particles of SARS-CoV-2, the virus that causes COVID-19, hide away in parts of the body, and the immune system becomes overactivated trying to eliminate them. The study has been reported in PLOS Pathogens.

    Colorized scanning electron micrograph of a cell (brown) infected with the Omicron strain of SARS-CoV-2 virus particles (purple), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

    Symptoms of long COVID can include fatigue, brain fog, cough, shortness of breath, and chest pain, and these symptoms last more than four weeks after the acute phase of COVID-19. The illness is thought to impact about 20 percent of people who get COVID, noted Brent Palmer, Ph.D., an associate professor at the University of Colorado School of Medicine.

    In this study, the researchers followed forty COVID-19 patients; twenty of them totally eliminated the infection and twenty developed long COVID, also known as  post-acute sequelae of COVID (PASC). The investigators used blood and stool samples from the study volunteers to identify T cells that were specific to COVID-19 and remained active after the initial infection was over.

    These cells were then incubated with bits of the virus, and the scientists were able to see how frequently CD4 and CD8 T cells were reacting by generating cytokines. They found that long COVID patients carried levels of cytotoxic CD8 T cells that were as much as 100 times higher compared to people who cleared the infection.

    Palmer also studies HIV infection, and he was astonished to find that about 50 percent of T cells were still directed against COVID-19 six months after their initial infection. “That’s an amazingly high frequency, much higher than we typically see in HIV, where you have ongoing viral replication all the time,” he added. “These responses were in most cases higher than what we see in HIV.”

    CU pulmonologist Sarah Jolley, MD was a study co-author who obtained pulmonary data for the study volunteers. The researchers found that pulmonary function decreased as the level of COVID-19-specific T cells increased.

    “That showed a really strong connection between these T cells that were potentially driving disease and an actual readout of disease, which was reduced pulmonary function. That was a critical discovery.”

    The researchers have suggested that long COVID is drive by the immune system, which is increasing inflammation as it attempts to remove residual SARS-CoV-2 particles that cannot be detected with a nasal swab, but nonetheless remain. Palmer noted that some autopsies of COVID-19 patients have revealed the virus in many organs including the lungs, gut and kidney.


    Additional work by Palmer and colleagues was reported in the journal Gut; this study indicated that the composition of the gut microbiomes of long COVID patients reflects an elevation of inflammatory markers. There may also be a link between the gut microbiome and the inflammation that is observed in long COVID, noted the researchers.

    Palmer added that some studies have shown that antiviral medications like Paxlovid, or doses of vaccine may help relieve the symptoms of long COVID patients. This may happen because their immune systems are being given enough of a stimulatory bump to finally remove the infection, and it would show that a hidden reservoir of virus likely exists in these patients.

    Sources: CU Anschutz Medical Campus, PLOS Pathogens, Gut

    Carmen Leitch

    Mushrooms are part of the world of fungi, and while they are often thought of as plants, they …

    Mushrooms are part of the world of fungi, and while they are often thought of as plants, they are in a class by themselves. Some mushrooms have more in common with animals than plants, such as a cholesterol-like molecule called ergosterol, and mushrooms have been called a “third food kingdom.” Edible fungi have been eaten in many cultures throughout history, which valued mushrooms for various reasons. Many edible mushrooms contain valuable nutrients including vitamin B6, selenium, potassium, and zinc. Other ‘poisonous’ mushrooms have psychoactive effects. Some studies have suggested that mushrooms have health benefits, like lowering high blood pressure, boosting immunity, keeping the heart healthy, and protecting the brain.

    Researchers found lion's mane mushroom improved brain cell growth and memory in pre-clinical trials. Image credit: UQ

    Now a study reported in the Journal of Neuroscience has identified a compound in a type of fungi called lion’s mane mushrooms (Hericium erinaceus) that can promote nerve growth and may enhance memory.

    While traditional Asian medicine has relied on lion’s mane mushroom extracts for centuries, noted Professor Frederic Meunier of the Queensland Brain Institute, the study authors wanted to use a scientific approach to examine the potential impact these extracts have on brain cells.

    Pre-clinical tests have suggested that lion’s mane mushrooms can improve memory and brain cell growth significantly. This study used neurons growing in culture to assess the effects of compounds that were isolated from those mushrooms. Active compounds were found to promote the extension of neuronal projections, noted Meunier, the corresponding study author.

    “Using super-resolution microscopy, we found the mushroom extract and its active components largely increase the size of growth cones, which are particularly important for brain cells to sense their environment and establish new connections with other neurons in the brain,” said Meunier.

    The study authors were aiming to find bioactive compounds in nature that are able to reach the brain, a sensitive organ that is protected by the selective blood-brain barrier, and influence neuronal growth and memory formation. These findings potentially have applications for the prevention or treatment of neurodegenerative diseases that affect cognition and memory, like Alzheimer’s disease, added study co-author Dr. Ramon Martinez-Marmol of the University of Queensland.

    Sources: University of Queensland, Journal of Neuroscience

    Carmen Leitch

    Even though humans are complex organisms and bacteria are single cells, and each are made of completely different …

    Even though humans are complex organisms and bacteria are single cells, and each are made of completely different cell types (eukaryotic and prokaryotic cells, respectively), there are some similar immune mechanisms at work in both of them. Scientists have now learned more about how a complex found in both human and bacterial cells, a group of enzymes called ubiquitin transferases, works to regulate immune pathways. The findings, which have been reported in Nature, may provide new insights into treatments for a wide range of human diseases, suggested the researchers.

    Image credit: Pixabay

    “This study demonstrates that we’re not all that different from bacteria,” said senior study author Aaron Whiteley, an assistant professor at the University of Colorado Boulder. “We can learn a lot about how the human body works by studying these bacterial processes.”

    Some research has suggested that the immune system found in humans has its origins in bacterial cells. Bacteria have to fight their own infections from other microbes like bacteriophages, viruses that infect bacterial cells. The CRISPR gene editing tool is derived from a bacterial immune defense.

    An enzyme called cGAS (cyclic GMP-AMP synthase) can be found in humans, and a simpler version of it is also carried by bacteria; cGAS works to activate an immune defense when viral pathogens are detected.

    Researchers have now analyzed the structure of bacterial cGAS, and revealed other proteins that are involved in the response to a viral infection. This study has shown that in bacteria, cGAS is modified by a simplified form of ubiquitin transferase, a crucial enzyme also found in human cells.

    Bacteria are far easier to manipulate genetically compared to human cells, so this opens up a world of new research opportunities, said co-first study author Hannah Ledvina, PhD, a postdoctoral researcher. “The ubiquitin transferases in bacteria are a missing link in our understanding of the evolutionary history of these proteins.”

    In this research, the scientists have also revealed two critical parts of ubiquitin transferase: Cap2 and Cap3 (CD-NTase-associated protein 2 and 3) that activate and deactivate the cGAS response, respectively.

    In humans cells, ubiquitin tags also work to mark cellular garbage, like dysfunctional or unnecessary proteins that have to be degraded and disposed. Problems with this system can lead to a buildup of cellular trash, which may lead to some disorders, such as neurodegeneration.

    Thus, while more research is needed, the study authors are hopeful that this work will enable us to learn more about many diseases, including autoimmune disorders like arthritis or neurodegenerative diseases such as Parkinson’s disease

    Parts of the bacterial ubiquitin transferase complex, like Cap3 – the off switch, could be harnessed to eliminate some pathologies related to human disease, suggested Whiteley.

    Sources: University of Colorado at Boulder, Nature

    Carmen Leitch

    Researchers have discovered that extracts from two different wild plants can each interfere with the ability of SARS-CoV-2, …

    Researchers have discovered that extracts from two different wild plants can each interfere with the ability of SARS-CoV-2, the virus that causes COVID-19, to infect cells. These findings, which utilized a cell culture model, come from a massive assessment of different botanical extracts. In this effort 1,800 extracts and 18 compounds were screened for efficacy against SARS-CoV-2. Flowers from tall goldenrod (Solidago altissima) plants and the stems of the eagle fern (Pteridium aquilinum) were each able to block SARS-CoV-2 from entering human cells. The work has been published in Scientific Reports.

    Colorized scanning electron micrograph of a cell (pink) infected with the Omicron strain of SARS-CoV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

    The study authors stressed that plants only contain miniscule amounts of the effective extracts, so it would be ineffective and possibly dangerous for people to attempt to self-medicate with the plants. They caution that eagle fern is known to be toxic.

    This work is promising, but it’s at the very early stages. The scientists are trying to find the molecules within the extracts that work against the virus. Once they are isolated, they will be tested to see if they are safe and can work against an actual infection, noted senior study author Cassandra Quave, an associate professor at Emory University.

    A rapid screening method was created for this study. SARS-CoV-2 uses its spike protein to latch onto ACE2 receptors on human cells and cause infection. The researchers engineered virus-like particles (VLPs) that mimicked the cell entry method of the pathogenic virus, but could not cause illness. Cells that had been engineered to express higher than usual levels of ACE2 receptors were exposed to these VLPs. If VLPs infected these cells, a green fluorescent protein signal was activated so the researchers could easily see how many cells were being infected.

    Plant extracts in Quave’s natural product library were introduced to the system to see which ones prevented infection. Tall goldenrod and eagle fern, which are native to North America and have been known as Native American traditional medicines, were found to have the highest activity against SARS-CoV-2 infection. These extracts were effective against the alpha, theta, delta and gamma variants of VLPs.

    The researchers also took the test a step further once the effective extracts were identified. With colleagues who have the biosecurity rating to work with infectious pathogens in the lab of study co-author and Emory professor Raymond Schinazi, the plant extracts were tested against the actual SARS-CoV-2 virus. This confirmed that tall goldenrod and eagle fern extracts can inhibit SARS-CoV-2 infection.

    “Our results set the stage for the future use of natural product libraries to find new tools or therapies against infectious diseases,” added Quave.

    Now the researchers want to figure out how the plant extracts are blocking the spike protein from binding to ACE2 receptors.

    Sources: Emory University, Scientific Reports


    Carmen Leitch

    The microbes of the world battle one another for domination, and some bacteria produce powerful molecules that can …

    The microbes of the world battle one another for domination, and some bacteria produce powerful molecules that can work against other microbes. Researchers have now discovered that some Pseudomonas bacteria generate strong antimicrobials that work against pathogenic fungi that affect humans, as well as plant fungal diseases. The findings have been reported in the Journal of the American Chemical Society.

    Image credit: Pixabay

    The chemicals that have been identified are called keanumycins, and these compounds can destroy a plant pest called Botrytis cinerea, which causes grey mold rot and leads to huge economic losses annually. Keanumycins can also inhibit pathogenic fungi that affect humans, including Candida albicans. Previous studies have indicated that it’s harmless to human and plant cells.

    Keanumycins may offer an environmentally friendly way to protect plants without using chemical pesticides. They may also be a weapon in the battle against drug-resistant fungi.

    “We have a crisis in anti-infectives,” noted first study author Sebastian Götze, a postdoc at Leibniz-HKI. “Many human pathogenic fungi are now resistant to antimycotics, partly because they are used in large quantities in agricultural fields.”

    The research team has been investigating Pseudomonas bacteria for a long time, and they know that many types of Pseudomonas are toxic to amoeba. The deadly effect of the bacteria is due to a few compounds that the investigators have traced to the Pseudomonas genome. The natural products are lipopeptides called keanumycins A, B and C, which have soap-like characteristics.

    One of those keanumycins was isolated so it could be studied further. “The lipopeptides kill so efficiently that we named them after Keanu Reeves because he, too, is extremely deadly in his roles,” quipped Götze.

    Some fungi have a resemblance to amoeba, and the researchers suspected keanumycins would also kill fungi. Indeed, tests reveled that Keanumycin could kill grey mould rot on hydrangea leaves. With only the fluid collected from a culture of bacterial, fungal growth slowed.

    Additional work will be needed to confirm the findings, but the liquid from Pseudomonas cultures could be used on plants, Götze noted.

    Keanumycin is also biodegradable, which suggests that permanent residues from the compound won’t contaminate soil, and it could be an environmentally friendly pesticide alternative.

    “In addition, we tested the isolated substance against various fungi that infect humans. We found that it strongly inhibits the pathogenic fungus Candida albicans, among others,” added Götze. There aren’t many antifungals on the market, so this would be a welcome addition to the pharmacy.

    Sources: Leibniz Institute for Natural Product Research and Infection Biology – Hans Knoell Institute, Journal of the American Chemical Society

    Carmen Leitch

    Researchers were able to take advantage of “an incredibly unique opportunity” to study the microbial life that rapidly …

    Researchers were able to take advantage of “an incredibly unique opportunity” to study the microbial life that rapidly colonized a short-lived island that formed in the South Pacific after a volcanic eruption. This work, reported in mBio, revealed a variety of unique microbes that could metabolize sulfur and gases in their local atmosphere, like the extremophile microbes that are sometimes found near hydrothermal vents or in hot springs. The lead author of a report on the findings, CIRES graduate student Nick Dragone noted that, “These types of volcanic eruptions happen all over the world, but they don’t usually produce islands.”

    Hunga Tonga-Hunga Ha'apai in 2017 / Image credit: NASA/Damien Grouille/Cecile Sabau

    But in 2015, an eruption of a submarine volcano created the Hunga Tonga Hunga Ha’apai Island, which existed for seven years. The formation of the island is described in the NASA video below. During the island’s lifetime, the study authors collected soil samples from the site and sent them off to the laboratory so that DNA in those samples could be extracted. By analyzing the genetic sequences, the scientists determined that some unusual bacteria were living on the island.

    The investigators said they were surprised by the findings. Instead of revealing organisms that accompany the retreat of glaciers, or marine microbes like cyanobacteria, they found something else — an unusual bunch of microbes that metabolize sulfur and atmospheric gases.

    On January 15, 2022, the research team got another surprise; there was another eruption near the island, which destroyed the entire landmass in the 21st century’s largest volcanic explosion (so far). Now, the site can’t be monitored ever again.

    “We were all expecting the island to stay,” said Dragone. “In fact, the week before the island exploded we were starting to plan a return trip.”

    Luckily the team was able to make use of the island while it existed. “No one had ever comprehensively studied the microorganisms on this type of island system at such an early stage before,” added Dragone.

    The short life of the island, and its volcanic origins, fostered an unusual community of microbes, as well as an international group of researchers working together. Learning more about this unique type of microbial community can provide insights into how ecosystems might start to develop, even before organisms like plants or animals arrive on the scene, noted corresponding study author and CIRES fellow Noah Fierer, a professor of ecology and evolutionary biology at CU Boulder.

    Sources: University of Colorado Boulder (CU Boulder) and Cooperative Institute for Research in Environmental Sciences (CIRES), mBio

    Carmen Leitch