Scientists discover a key molecular interaction in bacterial pathogens, opening the door for new treatment strategies

A science lab at UNLV.
Photo Credit: Josh Hawkins / University of Nevada, Las Vegas

The legendary Alexander Fleming, who famously discovered penicillin, once said “never to neglect an extraordinary appearance or happening.” And the path of science often leads to just that. New UNLV research is turning the page in our understanding of harmful bacteria and how they turn on certain genes, causing disease in our bodies.

A team of interdisciplinary scientists, led by professor and microbiologist Helen Wing, focuses on Shigella – a lethal bacterial pathogen that causes abdominal cramping, fever, and diarrhea. The Centers for Disease Control and Prevention estimates that Shigella cases lead to 600,000 deaths globally each year.

Shigella contains a major ‘switch’ protein (VirB), which triggers the bacterium to cause disease in humans. VirB does this by binding to Shigella’s DNA, activating the disease. The researchers showed that it is possible that interfering with VirB’s binding process can prevent Shigella from making us sick.

With a Proton Pump to More Growth

phytoplankton
Public Domain

An international research team with participation from Würzburg has discovered how algae compensate for nutrient deficiencies. Their discovery could help counteract the negative effects of climate change.

One of the building blocks of ocean life can adapt to cope with the effects of climate change, according to new research led by the University of East Anglia (UEA). The discovery holds promises for biotechnology developments that could counter the negative effects of changing environmental conditions, such as ocean warming and even the reduction in the productivity of crops.

Corresponding authors of the study, now published in the journal Nature Microbiology, are Thomas Mock, Professor of Marine Microbiology in the School of Environmental Sciences at UEA, and his former PhD student Dr. Jan Strauss. At Julius-Maximilians-Universität Würzburg (JMU), Professor Georg Nagel and Dr. Shiqiang Gao from the Department of Neurophysiology at the Institute of Physiology were involved.

Marine bacteria take a bite at plastic pollution

Plastic waste in the ocean is becoming a pressing issue.
Image Credit: rawpixel

A bacterium that can degrade the common polymer polybutylene succinate (PBS), which naturally biodegrades to only a limited extent in marine environments, could lead to improved ways to recycle this polymer. The bacterium’s potential, and its enzyme molecule that breaks down PBS, was discovered by researchers at Hokkaido University, working with colleagues at the Mitsubishi Chemical Group in Japan. The team published their results in the journal Environmental Microbiology.

PBS is generally regarded as an eco-friendly polymer due to its biodegradability when discarded on land and exposed to the atmosphere. This has led to its increasing use since the early 1990s in industrial plastics, including mulching films, compostable bags and catering packaging. But many discarded plastics eventually find their way into the sea, and unfortunately PBS does not biodegrade well in that environment.

“Plastic pollution in the ocean is a global problem and we need to tackle it by gaining new understanding of plastic behavior in that environment, and new technologies to deal with the pollution,” says Tomoo Sawabe, leader of the research team at Hokkaido University’s Faculty of Fisheries Sciences.

Thousands of programmable DNA-cutters found in algae, snails, and other organisms

Amoeba proteus with pseudopodia, cytoplasm often with truncated bipyramidal crystals
Image Credit: SmallRex
(CC BY-SA 4.0 DEED)

A diverse set of species, from snails to algae to amoebas, make programmable DNA-cutting enzymes called Fanzors — and a new study from scientists at MIT’s McGovern Institute for Brain Research has identified thousands of them. Fanzors are RNA-guided enzymes that can be programmed to cut DNA at specific sites, much like the bacterial enzymes that power the widely used gene-editing system known as CRISPR. The newly recognized diversity of natural Fanzor enzymes, reported in the journal Science Advances, gives scientists an extensive set of programmable enzymes that might be adapted into new tools for research or medicine.

“RNA-guided biology is what lets you make programmable tools that are really easy to use. So, the more we can find, the better,” says McGovern Fellow Omar Abudayyeh, who led the research with McGovern Fellow Jonathan Gootenberg.

CRISPR, an ancient bacterial defense system, has made it clear how useful RNA-guided enzymes can be when they are adapted for use in the lab. CRISPR-based genome editing tools developed by MIT professor and McGovern investigator Feng Zhang, Abudayyeh, Gootenberg, and others have changed the way scientists modify DNA, accelerating research and enabling the development of many experimental gene therapies.

A New Method for Assessing the Microbiome of the Human Gut

A technique called 'bead beating.'
Photo Credit: Courtesy of California Institute of Technology

The gut microbiome—the population and variety of bacteria within the intestine—is thought to influence a number of behavioral and disease traits in humans. Most obviously, it affects intestinal health. Cancer, inflammatory bowel disease, and celiac disease, for example, are all affected by the gut microbiome. But recent research at Caltech and other research centers has identified connections between the gut microbiome and diseases such as Parkinson's disease and multiple sclerosis as well as links between the gut microbiome and the presence of autistic behaviors, anxious behaviors, and a propensity to binge-eat sweets. (Most of this work has been done in the laboratory of Sarkis Mazmanian, Caltech's Luis B. and Nelly Soux Professor of Microbiology, who works mainly on mouse models.)

Looking directly at the human gut and the bacteria that make this space their home is often performed with sequencing—a process that analyzes the DNA sequences that make up each organism. However, this process is difficult in the intestine largely because the amount of microbial DNA in the gut is miniscule in comparison to the amount of host DNA. In intestinal tissue, roughly 99.99 percent of the DNA present is from the host organism; only 0.01 percent is microbial DNA.

However powerful the effects of these microbes, it is hard to understand their role without knowing their composition. Microbiome studies often rely on studies of feces and saliva, but these are quite different from the ecosystem of the gut itself.

Doubling Down on Known Protein Families

Shedding light on the diversity of microbial communities by looking at protein function within them.
Illustration Credit: Samantha Trieu/Berkeley Lab

Imagine researchers exploring a dark room with a flashlight, only able to clearly identify what falls within that single beam. When it comes to microbial communities, scientists have historically been unable to see beyond the beam – worse, they didn’t even know how big the room is.

A new study published online October 11, 2023 in Nature highlights the vast array of functional diversity of microbes through a novel approach to better understand microbial communities by looking at protein function within them. The work was led by a team of scientists at the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), and collaborators across multiple other research centers around the world.

“We’ve more than doubled the number of protein families known up until now, and identified many novel structure predictions,” said lead author on the paper Georgios Pavlopoulos, now a research director at the Biomedical Sciences Research Center Alexander Fleming. “This was a massive analysis of 1.3 billion proteins with massively parallel computations.”

Microbial Metabolites: A New Link to Parkinson's Disease?

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Researchers from the University of Vienna, University of Konstanz, and Albert Einstein College of Medicine uncover a potential environmental trigger for Parkinson's disease.

Published in Environment International, a groundbreaking study from the Institute of Biological Chemistry and Centre for Microbiology and Environmental Systems Science (CeMESS) at the University of Vienna, in collaboration with the University of Konstanz and the Albert Einstein College of Medicine, reveals a microbial metabolite's role in inducing Parkinson's-like symptoms. This discovery could reshape our understanding of the environmental triggers of Parkinson's disease.

The underlying causes of Parkinson's disease, a debilitating neurodegenerative condition, are not well understood. While genetic mutations are known to cause Parkinson's, a staggering 90% of cases are sporadic, with no clear genetic origin. Scientists suspect environmental factors could play a role – and substances like pesticides and industrial chemicals have been investigated for potential links to neurodegeneration. Among the possible culprits are microbial metabolites.

Recent studies highlight the gut-brain axis's importance, suggesting that our microbiome might influence neurodegenerative diseases. Notably, the gut microbiome of Parkinson's patients differs from that of healthy individuals. Some microbial metabolites have even been shown to specifically target dopamine-producing neurons, which are crucially affected in Parkinson's disease.

How plant-derived nutrients can affect the gut and brain

PD Dr. Veronica Witte
Photo Credit: Leipzig University/Antje Gildemeister

Can plant-derived nutrients alter gut bacteria to affect brain function? Scientists from the University of Leipzig Medical Center, the Max Planck Institute for Human Cognitive and Brain Sciences and the Helmholtz Centre for Environmental Research investigated this question in a study of overweight adults. Their findings, published in the journal Gut, suggest that dietary fiber can exert influence on both the composition of gut bacteria and the reward signals in the brain and associated food decision-making.

Prebiotics are used to foster the colonization of beneficial bacteria in the gut. These indigestible dietary fibers are found in plant-derived foods such as onions, leeks, artichokes, wheat, bananas, and in high concentrations in chicory root. They support gut health by promoting the growth and activity of beneficial gut bacteria. Researchers have now investigated whether certain prebiotics can also influence brain function by improving communication between the gut microbiome and the brain.

Red Algae Could Be Used to Create a Drug for Coronavirus

Chemical research on Laurencia red algae began in 1965.
Photo Credit: 🇸🇮 Janko Ferlič

Laurencia red algae can be used as a basis for new drugs against the SARS-CoV-2 virus, biochemists have found. A team of scientists from the Ural Federal University, the Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences, together with colleagues from Australia and Germany, carried out molecular docking of 300 bioactive components (ligands) of red algae and found seven compounds with the required activity. The scientists published a description of the experiments and results in the journal Microbiology Research. 

"Laurencia belongs to the family Rhodomelaceae, which is considered one of the largest families of marine red algae, with an estimated 125 genera and 700 species worldwide. Laurencia has recently been the subject of active research. Since 2015, a total of 1,047 secondary metabolites with various useful properties have been isolated from Laurencia species alone," explains Grigory Zyryanov, Chief Researcher of the UrFU Laboratory of Advanced Materials, Green Methods and Biotechnology.

Vacuum cleaner-effect in fungi can hold nanoplastics at bay

Photo Credit: Flockine

Using micro-engineered soil models, researchers at Lund University in Sweden have investigated the effect of tiny polystyrene particles on bacteria and fungi. While these nanoplastics reduced both bacterial and fungal growth, the fungus actually managed to "clean up" their surroundings, thereby easing the effect of the plastics.

“Plastic waste is a huge global problem. Whether carelessly discarded into nature, leaking from landfills or scoring from materials such as car tires and synthetic clothes – large amounts of micro- and nanoplastics end up in our soils,” says Micaela Mafla Endara, biology researcher at Lund University.

Nanoplastics have been proven to induce toxicity in diverse organisms, yet very little is known how this new pollutant is affecting the soil ecosystem. To study these nanoparticles of polystyrene, the researchers used microfluidic chips, a growth system that allowed them to observe interactions of single cells with the plastics under the microscope.

A mother mouse needs a diverse gut microbiome to form a healthy placenta

“More and more evidence is suggesting that [the gut microbiome] begins to exert its influence even during prenatal life,” said UCLA’s Elaine Hsiao.
Photo Credit: Karsten Paulick

The bacteria found naturally in the digestive tract does a lot more than help digest food.

Scientists have established that these microbial communities are also involved with the immune system and play a role in mental health. Now, they can add helping grow a healthy placenta during pregnancy to the list of unexpected ways the gut microbiome influences health and well-being.

New research led by UCLA scientists and published today in the journal Science Advances shows that mice with depleted gut microbiomes had smaller placentas than normal mice and that the network of blood vessels between the placenta and the fetus was also less developed.

Either of these conditions could deprive a fetus of nutrients, oxygen and other things it needs to grow. But when malnourished pregnant mice that had been fed low-protein diets and had diminished microbiomes were supplemented with short-chain fatty acids, which are produced by gut microbes, their placentas grew to normal size, the researchers said.

The new findings add to mounting evidence that in addition to its many other activities, the gut microbiome plays a role in the formation of new blood vessels, a process known as angiogenesis. They also show that byproducts of microbe metabolism known as metabolites play key roles in feto-placental development.

Strep Molecule Illuminates Cancer Immune Therapies

Colorized electron microscopy shows a chain of Streptococcus pyogenes bacteria between two immune cells.
Image Credit: National Institute of Allergy and Infectious Diseases

Researchers at Harvard Medical School have discovered that a molecule made by Streptococcus pyogenes — the bacterium that causes strep throat and other infections — could help explain several long-standing medical mysteries:

• Why strep sometimes leads to serious immune complications, including rheumatic fever.
• How the immune system's recognition of the molecule may contribute to diseases like lupus.
• Why one of the first cancer immunotherapies showed promise more than 100 years ago.
• How current immune therapies for cancer could be more effective.

The findings also contradict a long-standing belief that the immune system ignores this bacterial molecule and could propel efforts to tame or activate the immune system to treat a range of diseases.

The team, led by the lab of HMS biochemist Jon Clardy, published its findings in the Journal of the American Chemical Society.

“We were very surprised by the results, but the data were compelling,” said Clardy, the Christopher T. Walsh PhD Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS.

SARS-CoV-2 Caused More, Deadlier Cases of Sepsis Than Thought

Life-threatening systemic inflammation known as sepsis can follow infection with SARS-CoV-2 (shown in green in this colorized electron micrograph), the virus that causes COVID-19.
Image Credit: National Institute of Allergy and Infectious Diseases

New research suggests that the virus responsible for COVID-19 was a more common and deadly cause of sepsis early in the pandemic than previously assumed — accounting for about one in six cases of sepsis from March 2020 to November 2022.

The results, published online in JAMA Network Open, suggest that clinicians should rethink how they treat sepsis while also providing a framework for future surveillance of viral sepsis.

Sepsis is a serious, sometimes fatal overreaction of the immune system to an infection. Doctors and researchers don’t know as much about sepsis that occurs in response to viral infection as they do about sepsis that arises from bacterial infection.

“Most people, including medical professionals, equate sepsis with bacterial infections,” said first author Claire Shappell, HMS instructor in medicine at Brigham and Women’s Hospital. “This is reflected in treatment guidelines and quality measures that require immediate antibiotics for patients with suspected sepsis.”

How Tubular Bacterial Weapons Compromise Plant Cells to Cause Disease

An apple tree infected with fire blight reveals leaves that appear as if they were burned. HHMI Investigator Sheng Yang He and a team of researchers identified a plug-like molecule that could lead to new techniques to fight fire blight and other plant diseases.
Photo Credit: Sebastian Stabinger
(CC BY-SA 3.0.)

Some bacteria attack crops by delivering proteins that puncture the plant’s cell membranes, according to new research that explains the long-sought mechanism by which pathogens can release water within plant tissues, causing devastating infections.

In experiments first described in a preprint on bioRxiv and later published in Nature, a team led by plant microbiologist Sheng Yang He went a step further and found a way to block the holes the microbes make. Their research identified a plug-like molecule that showed potential for controlling diseases including fire blight, which can kill off apple and pear trees, leaving orchards looking as if they were burned.

“For 25 years, my lab and others have been trying to understand exactly how these bacterial proteins manipulate water within leaves,” says He, a Howard Hughes Medical Investigator at Duke University. “Now we have an answer: They open up channels through which water can move, disrupting plants’ internal water balance.”

Researchers have searched for this kind of detailed insight in hopes of opening the door to improved ways for fighting plant disease. Usually making such a connection can take years, if it is possible at all. However, He and his colleagues capitalized on this discovery quickly — using the dimensions of the pores to identify molecules perfectly sized for blocking them and protecting plants.

Wastewater detects signs of antimicrobial resistance in aged care

Photo Credit: Jsme MILA

A new study published today, analyzing wastewater samples from several aged care and retirement homes in Adelaide, has uncovered worrying signs of antimicrobial resistance (AMR) in at least one facility.

High levels of bacterial resistance against three common antibiotics – ceftazidime, cefepime and ciprofloxacin – were identified in one aged care residential home. A second facility recorded above average levels of antimicrobial resistance to gentamicin, putting residents’ health at risk.

The listed antibiotics are used to treat a variety of bacterial infections, including pneumonia, gynecological, urinary and respiratory tract infections, and those affecting bones and joints.

University of South Australia microbiologist, Associate Professor Rietie Venter, who led the study, says AMR is a concerning trend in aged care facilities.

“Antimicrobial resistance is projected to lead to 300 million deaths worldwide by 2060, and aged care residents are among the most vulnerable due to frequent, inappropriate use of medicines,” Assoc Prof Venter says.

Wearable sensor to monitor ‘last line of defense’ antibiotic

Sandia National Laboratories postdoctoral fellow Alex Downs places a wearable puck with microneedles under a microscope. Sandia researchers have combined earlier work on minimally invasive microneedles with nanoscale sensors to create a wearable sensor patch capable of continuously monitoring the levels of a ‘last line of defense’ antibiotic.
Photo Credit: Craig Fritz

Since the discovery of penicillin in 1928, bacteria have evolved numerous ways to evade or outright ignore the effects of antibiotics. Thankfully, healthcare providers have an arsenal of infrequently used antibiotics that are still effective against otherwise resistant strains of bacteria.

Researchers at Sandia National Laboratories have combined earlier work on painless microneedles with nanoscale sensors to create a wearable sensor patch capable of continuously monitoring the levels of one of these antibiotics.

The specific antibiotic they’re tracking is vancomycin, which is used as a last line of defense to treat severe bacterial infections, said Alex Downs, a Jill Hruby Fellow and project lead. Continuous monitoring is crucial for vancomycin because there is a narrow range within which it effectively kills bacteria without harming the patient, she added.

“This is a great application because it requires tight control,” said Philip Miller, a Sandia biomedical engineer who advised on the project. “In a clinical setting, how that would happen is a doctor would check on the patient on an hourly basis and request a single time-point blood measurement of vancomycin. Someone would come to draw blood, send it to the clinic and get an answer back at some later time. Our system is one way to address that delay.”

The researchers shared how to make these sensors and the results of their tests in a paper recently published in the scientific journal Biosensors and Bioelectronics.

Gut bacteria found in wild wolves may be key to improving domestic dogs’ health

Photo Credit: Nicky Pe

Gut microbes found in wild wolves may be the key to alleviating a debilitating gastrointestinal condition common to domestic dogs, according to a study led by researchers at Oregon State University – Cascades.

In a paper published in Applied Microbiology, the authors report a novel strain of Paenibacillus bacteria with characteristics of a probiotic – an organism that conveys a health benefit to the host.

In this case, the benefit would be to head off canine inflammatory bowel disease, a chronic illness characterized by vomiting, reduced appetite, weight loss, flatulence, a rumbling stomach and/or abdominal discomfort, said Bruce Seal of OSU-Cascades’ biology program.

“At present there is no known cure for this ongoing dysbiosis of the gastrointestinal tract, and there are limited options for treatment,” Seal said. “Underlying causes of the condition include an animal’s genetics, environmental factors, the immunological state of the GI tract and, maybe most importantly, an altered gut microbiome.”

Discrimination alters brain-gut ‘crosstalk,’ prompting poor food choices and increased health risks

Illustration Credit: julientromeur

People frequently exposed to racial or ethnic discrimination may be more susceptible to obesity and related health risks in part because of a stress response that changes biological processes and how we process food cues. These are findings from UCLA researchers conducting what is believed to be the first study directly examining effects of discrimination on responses to different types of food as influenced by the brain-gut-microbiome (BGM) system.

The changes appear to increase activation in regions of the brain associated with reward and self-indulgence – like seeking “feel-good” sensations from “comfort foods” – while decreasing activity in areas involved in decision making and self-control.

“We examined complex relationships between self-reported discrimination exposure and poor food choices, and we can see these processes lead to increased cravings for unhealthy foods, especially sweet foods, but also manifested as alterations in the bidirectional communication between the brain and the gut microbiome,” said Arpana Gupta, PhD, a researcher and co-director of the UCLA Goodman-Luskin Microbiome Center and the UCLA G. Oppenheimer Center for Neurobiology of Stress and Resilience.

Heavily mutated SARS-CoV-2 variant BA.2.86 not as resistant to antibodies as first feared

Image Credit: Fusion Medical Animation

Researchers at Karolinska Institutet who studied SARS-CoV-2 variant BA.2.86, found that the new variant was not significantly more resistant to antibodies than several other variants that are circulating. The study also showed that antibody levels to BA.2.86 were significantly higher after a wave of XBB infections compared to before, suggesting that the vaccines based on XBB should provide some cross-protection to BA.2.86.

"We engineered a spike gene that matches that of the BA.2.86 variant and tested the blood of Stockholm blood donors (specifically those donations made very recently) to see how effective their antibodies are against this new variant. We found that although BA.2.86 was quite resistant to neutralizing antibodies, it wasn't significantly more resistant than a number of other variants that are also circulating", says Daniel Sheward, lead author of the study and Postdoctoral researcher in Benjamin Murrell's team at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.

A lethal parasite’s secret weapon: infecting non-immune cells

Photomicrograph of spleen tissue showing the presence of numerous Leishmania donovani parasites in the amastigote form they take after infecting a host.
Image Credit: Centers for Disease Control and Prevention

The organisms that cause visceral leishmaniasis, a potentially deadly version of the parasitic disease that most often affects the skin to cause disfiguring disease, appear to have a secret weapon, new research suggests: They can infect non-immune cells and persist in those uncommon environments. 

Researchers found the Leishmania donovani parasites in blood-related stem cells in the bone marrow of chronically infected mice – precursor cells that can regenerate all types of cells in the blood-forming system. The finding may help explain why some people who develop visceral leishmaniasis, which is fatal if left untreated, often also have blood disorders such as anemia. 

Identifying these cells and other unexpected locations in which these parasites live improve scientists’ understanding of the disease and may lead to new treatment options, said senior study author Abhay Satoskar, professor of pathology in The Ohio State University College of Medicine.