Research reveals dual nature of beneficial bacteria UD1022

UD post-doctoral researcher Amanda Rosier is lead author on two papers reporting on the behavior of UD1022, a UD-patented beneficial bacteria that can help protect alfalfa from fungal pathogens.
Photo Credits: Evan Krape and courtesy of Amanda Rosie

Alfalfa, also known in Latin as Medicago sativa, is an agricultural crop that is part of the legume family. It is known as a protein-rich food source for dairy cattle that is easily digested and can lead to increased milk production. This is good news if you are a fan of ice cream or other dairy products. 

However, alfalfa can be susceptible to common fungal diseases, such as spring black stem or root rot, that can limit crop yields.

A recent paper published in Plants by University of Delaware plant biologist Harsh Bais and postdoctoral researcher Amanda Rosier has shown that UD1022, a UD-patented beneficial bacteria, can protect alfalfa plants from fungal pathogens that cause plant disease.

The UD-patented microbe UD1022 is a unique strain of Bacillus subtilis, a natural, beneficial bacterium that lives on the surface of roots and the surrounding soil, or rhizosphere. UD1022 is known as a growth promoter that can help plants flourish vigorously. It also is considered a plant protector for its ability to help plants wage a system-wide resistance when under attack by one of these microscopic disease agents.

Neutrons for better vaccines against multidrug resistant germs

Dr. Jia-Jheng Kang prepares measurements for the vaccines at the KWS-2 sample site.
Photo Credit: Bernhard Ludewig, FRM II / TUM

Neutrons from the Research Neutron Source Heinz Maier-Leibnitz (FRM II) can be used to explore the structure of biomolecules. The most recent success: the precise analysis of a promising vaccine against multidrug resistant germs.

Bacteria which are resistant to all conventional antibiotics cause more than a million deaths each year. Consequently, researchers around the world are searching for new therapeutic approaches to combat these pathogens. Two years ago, an international team in Grenoble identified an active ingredient suitable for the production of a vaccine against multidrug resistant bacteria Pseudomonas aeruginosa. The vaccine has in the meantime been successfully tested on mice.

"As with many new vaccines, in this case the active ingredient is embedded in liposomes. The exact characterization and understanding of these nanoscopic biomolecules is a key factor in the development and optimization of future vaccines," says Dr. Marco Maccarini, biophysicist at the French National Centre for Scientific Research (CNRS). Together with experts at the TIMC laboratory of the Université Grenoble Alpes (UGA) and at the FRM II he has successfully analyzed the structure of the candidate vaccine against Pseudomonas aeruginosa.

How the gut creates a cozy home for beneficial microbiome species

Image Credit: Courtesy of Carnegie Institution for Science

The digestive tract of fruit flies remodels itself to accommodate beneficial microbiome species and maintain long-term stability of the gut environment, according to new research led by Carnegie’s William Ludington and Allan Spradling. Their findings are published in Nature Communications.

The gut microbiome is an ecosystem of hundreds to thousands of microbial species living within the human body. These populations affect our health, fertility, and longevity. But there is still so much to learn about how these microbial species interact with our bodies and with each other.

“Every day, we encounter, and even ingest, a diverse array of bacterial species,” explained Ludington, who has been probing microbiome acquisition and composition for several years at Carnegie. “Despite this, the gut microbiome remains relatively stable over time—a phenomenon that is maintained across many species ranging from mammals to insects.”

He, Spradling, and their collaborators wanted to determine how our guts can maintain such remarkably consistent microbiome compositions. Because the human microbiome is so complex, they studied fruit flies, which are only colonized by a handful of microbial species.

ORNL-led team designs molecule to disrupt SARS-CoV-2 infection

Oak Ridge National Laboratory led a team of scientists to design a molecule that disrupts the infection mechanism of the SARS-CoV-2 coronavirus and could be used to develop new treatments for COVID-19 and future virus outbreaks.
Video Credit: Michelle Lehman/ORNL, U.S. Dept. of Energy

A team of scientists led by the Department of Energy’s Oak Ridge National Laboratory designed a molecule that disrupts the infection mechanism of the SARS-CoV-2 coronavirus and could be used to develop new treatments for COVID-19 and other viral diseases.

The molecule targets a lesser-studied enzyme in COVID-19 research, PLpro, that helps the coronavirus multiply and hampers the host body’s immune response. The molecule, called a covalent inhibitor, is effective as an antiviral treatment because it forms a strong chemical bond with its intended protein target.

“We’re attacking the virus from a different front, which is a good strategy in infectious disease research,” said Jerry Parks, who led the project and leads the Molecular Biophysics group at ORNL.

The research, detailed in Nature Communications, turned a previously identified noncovalent inhibitor of PLpro into a covalent one with higher potency, Parks said. Using mammalian cells, the team showed that the inhibitor molecule limits replication of the original SARS-CoV-2 virus strain as well as the Delta and Omicron variants.

HIV can persist for years in myeloid cells of people on antiretroviral therapy

HIV, the AIDS virus (yellow), infecting a human cell
Image Credit: National Cancer Institute

NIH-funded study confirms white blood cell subtype as HIV reservoir, suggests new target for cure efforts.

A subset of white blood cells, known as myeloid cells, can harbor HIV in people who have been virally suppressed for years on antiretroviral therapy, according to findings from a small study supported by the National Institutes of Health. In the study, researchers used a new quantitative method to show that HIV in specific myeloid cells—short-lived monocytes and longer-lived monocyte-derived macrophages—can be reactivated and infect new cells. The findings, published in Nature Microbiology, suggest that myeloid cells contribute to a long-lived HIV reservoir, making these cells an important but overlooked target in efforts to eradicate HIV.

“Our findings challenge the prevailing narrative that monocytes are too short-lived to be important in cure efforts,” said study author Rebecca Veenhuis, Ph.D., an assistant professor of molecular and comparative pathobiology and of neurology at Johns Hopkins University School of Medicine, Baltimore. “Yes, the cells are short-lived, but our follow-up data show that HIV can persist in monocytes over several years in people who are virally suppressed. The fact that we can detect HIV in these cells over such a long period suggests something is keeping the myeloid reservoir going.”

Understanding nitrogen metabolism could revolutionize TB treatment, finds study

Illustration Credit: Courtesy of University of Surrey

Development of new drugs to effectively target the bacterium that causes tuberculosis (TB) could be one step closer following an important discovery from the University of Surrey.

The Surrey study used a technology called fluxomics to reveal important information about how cells process nitrogen, which could help us better understand how harmful bacteria survive and cause disease. These findings have significant implications for studying the behavior and impact of pathogenic bacteria on human health.

In the most comprehensive study of its kind, the research team from Surrey conducted a study on the bacterium that causes tuberculosis, called Mycobacterium tuberculosis (Mtb). They wanted to understand how nitrogen is processed within Mtb cells, which is essential for the bacterium's survival. Surprisingly, previous studies had mostly examined the role of carbon in Mtb's survival, leaving the role of nitrogen poorly understood.

Wastewater could be the key to tracking more viruses than just COVID-19

Boehm lab graduate student Winnie Zambrana showing how wastewater samples are processed to test for evidence of viruses.
Photo Credit: Harry Gregory

Researchers have developed methods for using wastewater to track the levels of various respiratory viruses in a population. This can provide real-time information about virus circulation in a community.

Public health experts commonly track spikes in flu, respiratory syncytial virus (RSV), and rhinovirus circulating in a population through weekly reports from sentinel laboratories. These laboratories process samples from only severely ill patients, and it can take weeks for the results to get into the database. Now, for the first time, researchers at Stanford University, in collaboration with Emory University and Verily Life Sciences, have collected fast and accurate readings of a whole suite of respiratory viruses in their local Santa Clara sewer system.

Wastewater is currently the only source for accurate information about COVID-19 rates in communities. PCR testing is no longer widely available, and most people swab themselves at home where their results never reach public health agencies.

Prior to COVID-19, respiratory viruses had not been tracked through wastewater. Most of the viruses the scientists tested for in this study had never been measured in wastewater before. The findings are published in the March 22 issue of The Lancet Microbe.

Attack from the intestine

After an operation, bacteria can enter the organism from the intestine. Combat special cells of the immune system that are located in the liver.
Illustration Credit: Mercedes Gomez de Agüero

Darmbacteria are more common triggers of complications after surgery. This is shown by a new study by research teams from Würzburg and Bern. A solution to this problem could come from the liver.

German hospitals carried out almost 16 million operations in 2021. In Switzerland there are around 1.1 million. Even if the actual procedure is going well, it is not uncommon for a wound infection to occur afterwards, which can have dramatic consequences for those affected. In extreme cases, such infections are fatal.

A new study now shows that the causes of these infections are in a large part of the cases bacteria from the patient's intestine itself. To do this, the intestine does not even have to be injured during the operation. In this way, too, these pathogens overcome the intestinal barrier postoperatively and spread throughout the body through the blood and lymphatic pathways. They can be stopped by special immune cells that patrol all organs, including the liver.

Clues to the cause of chronic gut pain

Professor Stuart Brierley
Photo Credit: Courtesy of Flinders University

New insights into chronic gut pain offer hope for improved treatments for irritable bowel syndrome and anxiety treatment.

A research team led by Flinders University Professor Stuart Brierley, based at the SA Health and Medical Research Institute, with Nobel Laureate Professor David Julius, Professor Holly Ingraham and Dr James Bayrer at the University of California San Francisco, has shown evidence of a specific pathway of cells and nerves linking the gut to the brain that may be responsible for the chronic gut pain.

Chronic gut pain is commonly experienced by 11% of the global population currently living with irritable bowel syndrome (IBS) and associated psychological conditions, including anxiety and depression.

Described in a new article in Nature, the team used genetic and pharmacologic tools in pre-clinical models to manipulate signals between gut epithelial cells and associated nerve fibers to determine how this pathway stimulates chronic gut pain and anxiety.

Researchers develop a universal oral COVID-19 vaccine that prevents severe illness in hamsters

Illustration Credit: PIRO

A UCLA-led team has developed an inexpensive, universal oral COVID-19 vaccine that prevented severe respiratory illness and weight loss when tested in hamsters, which are naturally susceptible to SARS-CoV-2. It proved as effective as vaccines administered by injection or intranasally in the research.

If ultimately approved for human use, it could be a weapon against all COVID-19 variants and boost uptake, particularly in low- and middle-income countries, and among those with an aversion to needles.

The study is published in the peer-reviewed journal Microbiology Spectrum.

The oral vaccine is based primarily on the nucleocapsid protein, which is the most abundantly expressed of the virus’s four major structural proteins and evolves at a much slower rate than the frequently mutating spike protein. The vaccine utilizes a highly weakened bacterium to produce the nucleocapsid protein in infected cells as well as the membrane protein, which is another highly abundant viral structural protein.

Study Sheds Light on Ancient Microbial Dark Matter

Photo Credit: Apex 360

Bacteria are literally everywhere – in oceans, in soils, in extreme environments like hot springs, and even alongside and inside other organisms including humans. They’re nearly invisible, yet they play a big role in almost every facet of life on Earth.

Despite their abundance, surprisingly little is known about many microorganisms that have existed for billions of years.

This includes an entire lineage of nano-sized bacteria dubbed Omnitrophota. These bacteria, first discovered based on short fragments of DNA just 25 years ago, are common in many environments around the world but have been poorly understood. Until now.

An international research team produced the first large-scale analysis of more than 400 newly sequenced and existing Omnitrophota genomes, uncovering new details about their biology and behavior. The team’s findings are reported in the March 16 issue of the journal Nature Microbiology.

Dual immunotherapy plus chemotherapy before surgery improves patient outcomes in operable lung cancer

Tina Cascone, M.D., Ph.D., assistant professor of Thoracic/Head & Neck Medical Oncology
Photo Credit: Courtesy of University of Texas MD Anderson Cancer Center

In a Phase II trial led by researchers from The University of Texas MD Anderson Cancer Center, adding ipilimumab to a neoadjuvant, or pre-surgical, combination of nivolumab plus platinum-based chemotherapy, resulted in a major pathologic response (MPR) in half of all treated patients with early-stage, resectable non-small cell lung cancer (NSCLC).

New findings from the NEOSTAR trial, published today in Nature Medicine, provide further support for neoadjuvant immunotherapy-based treatment as an approach to reduce viable tumor at surgery and to improve outcomes in NSCLC. The combination also was associated with an increase in immune cell infiltration and a favorable gut microbiome composition.

The current study reports on the latest two arms of the NEOSTAR trial, evaluating neoadjuvant nivolumab plus chemotherapy (double combination) and neoadjuvant ipilimumab plus nivolumab and chemotherapy (triple combination). Both treatment arms met their prespecified primary endpoint boundaries of six or more patients achieving MPR, defined as 10% or less residual viable tumor (RVT) in the resected tumor specimen at surgery, a candidate surrogate endpoint of improved survival outcomes from prior studies.

Designing More Useful Bacteria

An illustration of viruses called phages infecting a bacterial cell.
Illustration Credit: Behnoush Hajian

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.

“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.

Research team proves bacteria-killing viruses deploy genetic code-switching to deceive hosts

ORNL scientists proved the theory that bacteria-destroying viruses called bacteriophages use genetic code-switching to first infect and later overwhelm their hosts.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

Scientists at the Department of Energy’s Oak Ridge National Laboratory have confirmed that bacteria-killing viruses called bacteriophages deploy a sneaky tactic when targeting their hosts: They use a standard genetic code when invading bacteria, then switch to an alternate code at later stages of infection.

Their study provides crucial information on the life cycle of phages. It could be a key step toward the development of new technologies such as therapeutics targeting human pathogens or methods to control phage-bacterial interactions in applications ranging from plant production to carbon sequestration.

Scientists have predicted since the mid-1990s that some organisms may use an alternate genetic code, but the process had never been observed experimentally in phages. ORNL researchers obtained the first experimental validation of this theory using uncultivated phages in human fecal samples and the lab’s high-performance mass spectrometry to reveal the intricacies of how phage proteins are expressed in the host organism. The work is detailed in Nature Communications.

Bypassing antibiotic resistance with a combination of drugs

A confocal microscopy image of macrophages treated with MTX (cyan) that have eaten bacteria (magenta)
Image Credit: © Singapore-MIT Alliance for Research and Technology (SMART)

By combining an antibiotic with an anti-cancer agent, an international team has developed a treatment capable of circumventing the antibiotic resistance of the bacterium Enterococcus faecalis.

Antibiotic resistance is one of the world’s most pressing health challenges: in 2019, nearly 5 million people died from an infection associated with or attributed to antibiotic resistance. A research consortium involving the Singapore-MIT Alliance for Research and Technology (SMART), the Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University (NTU), the Massachusetts Institute of Technology (MIT) and the University of Geneva (UNIGE) has tackled the potentially deadly Enterococcus faecalis bacterium, most strains of which have developed resistance to common antibiotics. The scientists have developed an innovative strategy that consists of adding mitoxantrone, an anti-cancer agent, to vancomycin, the main antibiotic used in this context. The combination of these two drugs targets simultaneously the bacteria and the human immune system, and circumvents resistance. These promising results can be read in the journal Science Advances.

Rice labs seek RNA programming for ‘smart’ antibiotics

Rice University bioscientists James Chappell (left) and Joff Silberg aim to create “genetically encoded antibiotics,” strands of RNA that bacteria will readily copy and share. The RNA will selectively kill disease-causing bacteria thanks to a triggering mechanism that will be activated by “virulence genes” or other biomarkers found only in bacterial pathogens.
Photo Credit: Jeff Fitlow/Rice University

Synthetic biologists at Rice University are embarking on a three-year project to create “genetically encoded antibiotics,” strands of RNA that bacteria will readily copy and share that will selectively kill only disease-causing, pathogenic bacteria.

“Most bacteria pose no danger to human health,” said James Chappell, an assistant professor of biosciences and bioengineering at Rice. “The question for us as synthetic biologists is, ‘Can we create genetic programs that move through microbial communities and precisely remove only the bad actors from those communities?’”

Thanks to a $1.5 million grant from the Kleberg Foundation, Chappell’s lab and the lab of Rice bioscientist and bioengineer Jonathan “Joff” Silberg are getting a chance to test their idea of combating antibiotic resistance by enlisting the aid of bacteria that either benefit humans or pose no threat to them.

In prototype tests, they showed they could design RNA programs that were highly targeted and potent, killing 99.99% of “bad actor” pathogens within a matter of hours. In the three-year project, they also plan to partner with Dr. Pablo Okhuysen from the University of Texas MD Anderson Cancer Center to design RNA antibiotics that are effective against diarrhea-causing E. coli, as well as RNA drugs that selectively kill the opportunistic Lactobacillus iners, a pathogen that has been associated with cervical cancer radiation therapy resistance.

Deeper insights into bacteria

Image Credit: NCI

RNA sequencing technologies provide valuable insights into how individual cells work. A research team at the University of Würzburg has now developed a technique that provides an even more detailed view.

How do cells work in a normal state? How do they change when they cause disease? Do they react as desired to new drugs? Nowadays, anyone seeking answers to these – and other related – questions in the laboratory can hardly do without a special technique: single-cell RNA sequencing, or "scRNA-seq" for short. This technique provides an accurate picture of gene expression in a single cell at a specific point of time, as well as the associated regulatory networks, allowing conclusions to be drawn about the molecular basis of cell activity.

A research team at the Julius-Maximilians-Universität Würzburg (JMU) has now further improved a single-cell RNA sequencing technique it previously developed for use in bacteria. This means that the work in the laboratory is even faster than before and provides much more precise information. The team presents its development in the journal mBio.

How Do Microbes Live Off Light?

Prof. Oded Béjà (left) and PhD student Ariel Chazan
Photo Credit: Technion-Israel Institute of Technology

Plants convert light into a form of energy that they can use – a molecule called adenosine triphosphate (ATP) – through photosynthesis. This is a complex process that also produces sugar, which the plant can use for energy later, and oxygen. Some bacteria that live in the light-exposed layers of water sources can also convert light to ATP, but the process they use is simpler and less efficient than photosynthesis. Nonetheless, Technion – Israel Institute of Technology researchers now find this process isn’t as straightforward and limited as was previously thought.

Rhodopsin are the light-driven proton pumps that bacteria employ to produce ATP. Whereas photosynthesis is a process that involves multiple stages and proteins, rhodopsin performs everything itself. It is not more efficient, but rather it is like the difference between a medieval workshop and a modern factory. The rhodopsin's are activated by a molecule called “retinal,” which absorbs light. Specifically, in these proteins retinal absorbs green light. A different molecule, a carotenoid “antenna,” can enable it to also absorb blue light as well, increasing the amount of energy the rhodopsin can produce.

Pseudomonas aeruginosa Bacteria produce a molecule that paralyzes immune system cells

Human endothelial cells use the molecules cadherin (green) and actin (purple) to form a flexible barrier around blood vessels. After adding the isolated LecB, their localization in the cell changes significantly: in the right half of the image, cadherin is no longer on the outside of the cell, but near the nucleus (blue).
Image Credit: Yubing Guo / Universities of Freiburg and Strasbourg

Bacteria of the species Pseudomonas aeruginosa are antibiotic-resistant hospital germs that can enter blood, lungs and other tissues through wounds and cause life-threatening infections. In a joint project, researchers from the Universities of Freiburg and Strasbourg in France have discovered a mechanism that likely contributes to the severity of P. aeruginosa infections. At the same time, it could be a target for future treatments. The results recently appeared in the journal EMBO Reports.

Many bacterial species use sugar-binding molecules called lectins to attach to and invade host cells. Lectins can also influence the immune response to bacterial infections. However, these functions have hardly been researched so far. A research consortium led by Prof. Dr. Winfried Römer from the Cluster of Excellence CIBSS - Centre for Integrative Biological Signaling Studies at the University of Freiburg and Prof. Dr. Christopher G. Mueller from the IBMC - Institute of Molecular and Cell Biology at the CNRS/University of Strasbourg has investigated the effect of the lectin LecB from P. aeruginosa on the immune system. It found that isolated LecB can render immune cells ineffective: The cells are then no longer able to migrate through the body and trigger an immune response. The administration of a substance directed against LecB prevented this effect and led to the immune cells being able to move unhindered again.

In the end, it's the individual advantage that counts

The three phases of exceptional dynamics: (1) Predation on the unprotected bacteria by predators, (2) toxin formation as cooperative defense and recovery of the bacterial population, (3) filament formation as individual defense through evolution and stabilization of densities.
Photo Credit: David Kneis/TU Dresden

Bacteria rely on cooperation and evolution in order to defend themselves against predatory protists

Eating and being eaten is a normal process in nature. These predator-prey dynamics help to stabilize ecosystems. It ensures that individual species do not become too abundant, controls their populations, and prevents damage caused by overpopulation (e.g., browsing by deer in the forest or damage to crops by caterpillars). But how is it that the predators do not simply eat away all the prey, thus breaking down the system? A research team from the Helmholtz Centre for Environmental Research (UFZ) together with scientists from the Technical University (TU) of Dresden and the University of Potsdam has investigated this using bacteria and protists that live in bodies of water and discovered something astonishing. According to an article recently published in ISME Journal, bacteria defend themselves against predatory protists with cooperative behavior and evolution.

In a lake or river, between one and 10 million bacteria live in just 1 ml of water. Such a high density is necessary because bacteria permanently break down organic compounds and pollutants and thus purify the water. However, if there are too many bacteria, this can lead to the spread of pathogens. Preventing this requires predators: microscopic protists of which there are usually between a few hundred and a few thousand individuals in 1 ml of water. They constantly eat bacteria and thus ensure that the bacteria fulfil their cleaning function but do not become too abundant. Using the bacterium Pseudomonas putida and the bacterivorous protist Poteriospumella lacustris, the research team investigated the role of the various defense strategies of the bacteria and how the formation of feeding resistance is related to the dynamics of ecological systems.