Better diagnosis and treatment of cryptococcosis

Photo Credit: Courtesy of University of Cologne

Global guideline for the management of cryptococcosis, a fungal infection that can have serious health consequences, published in the journal ‘The Lancet Infectious Diseases’

A group of international mycology experts led by Professor Dr Oliver A. Cornely at the University of Cologne has jointly drafted a guideline for the diagnosis and treatment of cryptococcosis, which aims at improving infection management and thus the survival rate of patients. Cryptococcosis is a fungal infection of mainly the lungs that might lead to meningitis. The article ‘Global guideline for the diagnosis and management of cryptococcosis’ was published in the journal The Lancet Infectious Diseases.

Cryptococcosis, especially cryptococcal meningitis (CM) as the most fatal form, is responsible for a high fatality rate among patients. It is one of the most widespread invasive fungal infections in the world and is a major threat particularly to people suffering from immunodeficiencies. For example, around one million cases of cryptococcal meningoencephalitis are diagnosed worldwide every year in people with HIV alone, and more than 600,000 people die from the disease each year. Patients who have undergone a bone marrow transplant or organ transplant are also at high risk of infection. It is transmitted through the inhalation of spores from soil. Other organs are then also infected via the bloodstream. The lungs, brain, skin and bones are most frequently affected.

Compounds released by bleaching coral reefs promote bacteria

Field site in Moʻorea, French Polynesia.
Photo Credit: Milou Arts of NIOZ

On healthy reefs, corals, algae, fishes and microbes live interconnected and in balance—exchanging nutrients, resources and chemical signals. New research led by the University of Hawaiʻi at Mānoa and the Royal Netherlands Institute for Sea Research (NIOZ) revealed that when coral bleaching occurs, corals release unique organic compounds into the surrounding water that not only promote bacterial growth overall, but also promote bacteria that may further stress reefs and pose the risk for more damage.

“Our results demonstrate how the impacts of both short-term thermal stress and long-term bleaching may extend beyond coral and into the water column,” said Wesley Sparagon, co-lead author, postdoctoral researcher in the UH Mānoa College of Tropical Agriculture and Human Resources and previous doctoral student with the UH Mānoa School of Ocean and Earth Science and Technology (SOEST).

The research team, which included scientists from UH Mānoa, NIOZ, Scripps Institution of Oceanography and University of California, Santa Barbara, conducted experiments on bleached and unbleached corals gathered during a bleaching event in Moorea, French Polynesia in 2019.

“Although coral bleaching is a well-documented and increasingly widespread phenomenon in reefs across the globe, there has been relatively little research on the implications for reef water column microbiology and biogeochemistry,” said Craig Nelson, senior author on the study and professor in SOEST.

Multitasking microbes: UW–Madison scientists engineer bacteria to make two valuable products from plant fiber

Ben Hall, Genetics Ph.D. Student, holds a mixed sample of microbes and carotenoids, in Tim Donohue’s lab.
Photo Credit: Chelsea Mamott

We often look to the smallest lifeforms for help solving the biggest problems: Microbes help make foods and beverages, cure diseases, treat waste and even clean up pollution. Yeast and bacteria can also convert plant sugars into biofuels and chemicals traditionally derived from fossil fuels — a key component of most plans to slow climate change.

Now University of Wisconsin–Madison researchers have engineered bacteria that can produce two chemical products at the same time from underutilized plant fiber. And unlike humans, these multitasking microbes can do both things equally well.

“To my knowledge, it’s one of the first times you can make two valuable products simultaneously in one microbe,” says Tim Donohue, UW–Madison professor of bacteriology and director of the Great Lakes Bioenergy Research Center.

The discovery, detailed in a paper in the December issue of the journal Applied and Environmental Microbiology, could help make biofuels more sustainable and commercially viable.

“In principle, the strategy lowers the net greenhouse gas emissions and improves the economics,” Donohue says. “The amount of energy and greenhouse gas that you need to make two products in one pot is going to be less than running two pots to make one product in each pot.”

Discovery: plants use “trojan horse” to fight mold invasions

Photo Credit: Gábor Adonyi

UC Riverside scientists have discovered a stealth molecular weapon that plants use to attack the cells of invading gray mold. 

If you’ve ever seen a fuzzy piece of fruit in your fridge, you’ve seen gray mold. It is an aggressive fungus that infects more than 1,400 different plant species: almost all fruits, vegetables, and many flowers. It is the second most damaging fungus for food crops in the world, causing billions in annual crop losses.

A new paper in the journal Cell Host & Microbe describes how plants send tiny, innocuous-seeming lipid “bubbles” filled with RNA across enemy lines, into the cells of the aggressive mold. Once inside, different types of RNA come out to suppress the infectious cells that sucked them in.

“Plants are not just sitting there doing nothing. They are trying to protect themselves from the mold, and now we have a better idea how they’re doing that,” said Hailing Jin, Microbiology & Plant Pathology Department professor at UCR and lead author of the new paper.

Previously, Jin’s team discovered that plants are using the bubbles, technically called extracellular vesicles, to send small RNA molecules able to silence genes that make the mold virulent. Now, the team has learned these bubbles can also contain messenger RNA, or mRNA, molecules that attack important cellular processes, including the functions of organelles in mold cells. 

Giant bacterium powers itself with unique processes

Micrograph of a group of Epulopiscium viviparus bacteria.
Image Credit: Esther Angert

Not all bacteria are created equal.

Most are single-celled and tiny, a few ten-thousandths of a centimeter long. But bacteria of the Epulopiscium family are large enough to be seen with the naked eye and 1 million times the volume of their better-known cousins, E. coli.

In a study published Dec. 18 in Proceedings of the National Academy of Sciences, researchers from Cornell and Lawrence Berkeley National Laboratory have for the first time described the full genome of one species of the family of giants, which they’ve named Epulopiscium viviparus.

“This incredible giant bacterium is unique and interesting in so many ways: its enormous size, its mode of reproduction, the methods by which it meets its metabolic needs and more,” said Esther Angert, professor of microbiology in the College of Agriculture and Life Sciences, and corresponding author of the study. “Revealing the genomic potential of this organism just kind of blew our minds.”

The first member of the Epulopiscium family was discovered in 1985. All members of the species live symbiotically within the intestinal tracts of certain surgeonfish in tropical marine coral reef environments, such as the Great Barrier Reef and in the Red Sea.

Genetic sequencing uncovers unexpected source of pathogens in floodwaters

A NASA image containing visible and infrared data revealing the presence of dissolved organic matter – including potential antibiotic-resistant pathogens – in the waterways along coastal North Carolina after Hurricane Florence.
Image Credit: Courtesy NASA

Researchers report in the journal Geohealth that local rivers and streams were the source of the Salmonella enterica contamination along coastal North Carolina after Hurricane Florence in 2018 – not the previously suspected high number of pig farms in the region. 

These findings have critical implications for controlling the spread of disease caused by antibiotic-resistant pathogens after flooding events, particularly in the coastal regions of developing countries that are being highly impacted by the increase in tropical storms. 

The study, led by civil and environmental engineering professor Helen Nguyen and graduate student Yuqing Mao, tracks the presence and origin of S. enterica from environmental samples from coastal North Carolina using genetic tracing. 

“Infections caused by antibiotic-resistant pathogens are responsible for approximately 2.8 million human illnesses and 36,000 deaths per year in the U.S. alone,” Nguyen said. “These infections spread easily across the globe and are a major burden on burgeoning health care systems, but they are preventable through mitigation.”

Dramatic rise in antibiotic use in first year of pandemic in primary care

Excessive use of antibiotics can give rise to bacterial resistance to these drugs, making bacterial infections increasingly hard to treat
Image Credit: Arek Socha

Antibiotics have no effect on viruses, and that includes the coronavirus. Yet in the first year of the pandemic, primary care physicians in Switzerland prescribed antibacterial medications twice as frequently as before, report researchers at the University of Basel. A risky practice, warns the research team.

It was a time of great uncertainty. When the first wave of the new coronavirus swept across Switzerland in winter and spring 2020, there were no diagnostic tests, no vaccines, and no effective medications. During this precarious phase, primary care physicians based in Switzerland seem to have increasingly resorted to treating patients with antibiotics, even though these medications have no effect on viruses. This was the conclusion reached by a research team led by Professor Heiner C. Bucher from the Department of Clinical Research at the University of Basel and University Hospital Basel.

As the team reports in the journal Clinical Microbiology and Infection, the use of antibiotics doubled from around eight to 16 prescriptions per 100 consultations. During the first wave of SARS-CoV-2 at the beginning of 2020, a massive rise in prescriptions of antibiotics became apparent. Prescriptions then remained at an above-average level throughout the year compared with previous years (2017-2019).

New possibilities for a healing toxin

Richard Kammerer and Oneda Leka in one of the PSI laboratories in front of an apparatus that is used, among other things, to purify proteins.
Photo Credit: Paul Scherrer Institute/Mahir Dzambegovic

PSI researchers have discovered a surprising trick that could expand the possibilities for medical use of botulinum toxin A1, better known under the name Botox, as an active agent. They have developed antibody-like proteins that speed up the enzyme’s effect on the transmission of nerve signals. This suggests that Botox might, for example, be able to relief pain more quickly than before. The study has now been published in the journal Nature Communications.

Botulinum neurotoxin A1, better known under the trademark Botox, is actually a nerve toxin produced by bacteria. It gained widespread public awareness through its use as a cosmetic aid. Many people have it injected into wrinkles to make them look younger. The substance blocks signal transmission from nerves to muscles, thus relaxing them so that facial features appear smooth. What is less well known: Botox is also used very often in therapeutic medicine to treat conditions that can be traced back to cramping muscles or faulty nerve signals, including pains, spasms, bladder weakness, grinding of teeth, and misalignments, for example of the eyes. Botox is even used in treating stomach cancer, to block the vagus nerve and thus slow down tumor growth.

In any therapy, it is crucial to use this highly effective medicine in a very targeted manner with careful dosage, since Botox is the most potent natural nerve toxin of all, which can lead to dangerous paralysis in a clinical picture called botulism. Just one hundred nanograms or so administered intravenously can be enough to kill a person, because the toxin paralyses the respiratory muscles, along with others.

The keto diet protects against epileptic seizures. Scientists are uncovering why

Photo Credit: Jenna Hamra

The high-fat, low-carbohydrate ketogenic diet is more than just a trendy weight-loss tactic. It has also been known to help control seizures in children with epilepsy, particularly those who don’t respond to first-line anti-seizure medications.

In a new UCLA study published in the journal Cell Reports, researchers demonstrate that the changes the diet causes in the human gut microbiome — the trillions of bacteria and other microorganisms that live in the digestive tract — can confer protection against seizures in mice.

Understanding how the function of the microbiome is altered by the diet could aid in the development of new therapeutic approaches that incorporate these beneficial changes while avoiding certain drawbacks of the diet, said the study’s lead author, Gregory Lum, a postdoctoral researcher in the laboratory of UCLA professor Elaine Hsiao.

The ketogenic diet is not recommended as a primary anti-seizure option because patients are often averse to drastic changes in their food intake or have trouble staying on the diet due to its strict requirements and potential side effects like, nausea, constipation and fatigue.

Revealed: Some microbiome species regulate their entire bacterial ecosystem

Image Credit: Scientific Frontline 

A team of mathematicians and biologists led by Carnegie’s Will Ludington and Technische Universität Berlin’s Michael Joswig developed a new approach to reveal key genes and species that regulate biological networks. Their work, published this week in Proceedings of the National Academy of Sciences, identifies genes in cells and species in ecosystems that sit at the top of a regulatory hierarchy and drive evolutionary and ecological trajectories.

Charles Darwin concluded On the Origin of Species with the famous “tangled bank” analogy to explain how organisms in an ecosystem affect one another’s fitness. “It is interesting to contemplate a tangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth,” Darwin wrote. “And to reflect that these elaborately constructed forms, so different from each other, and dependent upon each other in so complex a manner, have all been produced by laws acting around us.” 

To map these interactions in ecosystems, ecologists use network analysis to study the connections. Keystone species, such as wolves, have a disproportionately large impact on their communities and the other organisms within them.

Ribosomal protein exhibits remarkable evolutionary transformation

The cryo-EM maps and atomic models showing the structure of ribosomal protein msL1 in the ribosome from microsporidian parasites V. necatrix (first row), and protein msL2 in the ribosome from microsporidian parasites E. cuniculi (second row).
Illustration Credit: Leon Schierholz

A team of researchers from the Universities of Newcastle and Umeå has discovered that a ribosomal protein exhibits a remarkable evolutionary transformation, with its three-dimensional structure changing drastically while its sequence remains relatively conserved.

The protein, known as msL1/msL2, is found in ribosomes of parasitic microorganisms called microsporidia, and it is suggested to play a role in stabilizing the highly reduced protein synthesis machinery in these unique organisms. 

“Despite its conserved sequence, msL1/msL2 adopts distinct folds in two different microsporidian species, Encephalitozoon cuniculi, and Vairimorpha necatrix. This structural divergence is particularly striking given that the two proteins share approximately 41% sequence similarity,” comments Léon Schierholz, one of the authors from Umeå University.  

Protein study could one day advance Parkinson’s, breast cancer care

Jonathan Pruneda, Ph.D., led a study to explore how a form of the common protein ubiquitin is modified during an infection with illness-causing bacteria. With further research, his study's findings could lead to improved care for Parkinson's disease and breast cancer.
Photo Credit: OHSU/Christine Torres Hicks

New research from Oregon Health & Science University could one day lead to therapies that prevent or treat diseases and infections tied to a protein that’s found in all human cells.

A study published today in the journal Molecular Cell describes how the protein ubiquitin is modified during a bacterial infection. The study details the steps taken to create a form of the protein known as lysine 6 polyubiquitin, where a long chain of ubiquitin molecules are linked through the amino acid lysine. This form of ubiquitin helps cells communicate by sending a molecular message — communication that remains poorly understood.

Previous research has indicated that this form of ubiquitin may be linked to the development of Parkinson’s disease and breast cancer. However, the details of how lysine 6 polyubiquitin is formed or how it is involved in disease aren’t yet clear.

To explore this, OHSU scientists turned their attention to illness-causing bacteria and how they manipulate lysine 6 polyubiquitin during infection. Researchers isolated enzymes used by E. coli and Salmonella to cause food poisoning and other illnesses, and observed how the enzymes interacted with ubiquitin.

New antifungal molecule kills fungi without toxicity in human cells, mice

The mechanism for a critical but highly toxic antifungal is revealed in high resolution. Self-assembled Amphotericin B sponges (depicted in light blue) rapidly extract sterols (depicted in orange and white) from cells. This atomic level understanding yielded a novel kidney-sparing antifungal agent. 
Illustration Credit: Jose Vazquez

A new antifungal molecule, devised by tweaking the structure of prominent antifungal drug Amphotericin B, has the potential to harness the drug’s power against fungal infections while doing away with its toxicity, researchers at the University of Illinois Urbana-Champaign and collaborators at the University of Wisconsin-Madison report in the journal Nature.

Amphotericin B, a naturally occurring small molecule produced by bacteria, is a drug used as a last resort to treat fungal infections. While AmB excels at killing fungi, it is reserved as a last line of defense because it also is toxic to the human patient – particularly the kidneys. 

Scientists engineer potent immune cells for ‘off-the-shelf’ cancer immunotherapy

Illustration Credit: Scientific Frontline

UCLA scientists have developed a new method to engineer more powerful immune cells that can potentially be used for “off-the-shelf” cell therapy to treat challenging cancers.

“Off-the-shelf” cell therapy, also known as allogenic therapy, uses immune cells derived from healthy donors instead of patients. The approach can bring cell therapies, like chimeric antigen receptor (CAR) T cell therapy, to more patients in a timelier manner, which is one of the major barriers in getting these life-saving treatments to patients.

“Time is often of the essence when it comes to treating people with advanced cancers,” said Lili Yang, associate professor of microbiology, immunology and molecular genetics and member of the UCLA Health Jonsson Comprehensive Cancer Center. “Currently, these types of therapies need to be tailored to the individual patient. We have to extract white blood cells from a patient, genetically engineer the cells and then re-infuse them back into the patient. This process can take weeks to months and can cost hundreds of thousands of dollars to treat each patient.”

Predatory Bacteria

Predatory bacteria such as B. bacteriovorus attack and neutralize other types of bacteria.
Illustration Credit:: Benjamin Güdel

Antibiotic resistance is increasingly becoming a challenge for treating bacterial infections. Microbiologist Simona Huwiler is researching whether predatory bacteria — that is, bacteria that eat other bacteria — can be used as a new kind of antibiotic and whether this approach also leads to the development of resistance.

The spread of antibiotic-resistant bacteria is an enormous challenge for the healthcare system. It is almost impossible to stop the development of antimicrobial resistance, and there are almost no new kinds of antibiotics being developed that can be used against drug-resistant bacteria. Researchers are therefore looking to nature to find alternatives. They have set their sights on the natural enemies of pathogenic bacteria such as bacteriophages – viruses that kill bacteria – as well as predatory bacteria that attack, consume and eliminate other types of bacteria. Bdellovibrio bacteriovorus is one type of predatory bacteria that is of interest to researchers. It’s an ideal candidate because it likes to dine on gram-negative bacteria with antibiotic resistance. Experiments in the lab have shown that Bdellovibrio bacteriovorus is capable of killing and eating many kinds of pathogenic bacteria, including Escherichia coli, Enterobacter, Proteus, Serratia, Citrobacter, Yersinia, Shigellen, Salmonella and Vibrio. This varied meal plan is an advantage compared to bacteriophages, which usually prefer to eat one specific kind of bacteria.

New antibodies neutralize resistant bacteria

Cryo-electron microscopic reconstruction of the binding of a human anti-PcrV Fab antibody (yellow) to a PcrV pentamer (blue) of the type III secretion system (T3SS) of Pseudomonas aeruginosa. The antibody binding leads to an inhibition of the T3SS, which is an important virulence factor of P. aeruginosa.
Image Credits: CSSB/Biao Yuan

A research team has discovered antibodies that could lead to a new approach to treating acute and chronic infections with the bacterium Pseudomonas aeruginosa. Due to its numerous resistance mechanisms, P. aeruginosa is associated with high morbidity and mortality and can cause complicated infections and dangerous cases of sepsis in severely ill patients. The team of scientists from the University of Cologne, University Hospital Cologne, the Helmholtz Centre for Infection Research in Braunschweig and University Hospital Hamburg-Eppendorf isolated the antibodies from immune cells of chronically ill patients and described their binding mechanisms. The study ‘Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa’ was published in the renowned scientific journal Cell.

Antibiotic-resistant bacteria are a crucial health concern worldwide not only to infected people, but also to our healthcare systems in general. Infections with the bacterium P. aeruginosa in particular are a threat due to numerous resistance mechanisms, often leading to complicated infections of the lungs and dangerous sepsis, especially in severely ill patients. In addition, the pathogen can permanently colonize organs such as the lungs, where it promotes progressive tissue damage. Often, so-called last-resort antibiotics must be used to treat infected patients, as the standard treatments no longer work. New therapeutic approaches are therefore urgently needed to ensure effective treatment for infections with multi-resistant pathogens such as P. aeruginosa in the future.

New study: Deep-sea pressure preserves food for microbes in the abyss

A flake of marine snow from the experiment.
Photo Credit: © Peter Stief/SDU

A new study from the Danish Center for Hadal Research reports on a series of experiments with exposing marine snow to increasing pressure - up to 1000 bar, which corresponds to the pressure at the bottom of some of the world's deep-sea trenches, 10 km below the sea surface.

Marine snow is millimeter-sized flakes, created when sticky, dead cells at the sea surface clump together with other dead or dying cells, particles and bacteria and sink to the bottom. The organic material can be dead algae, dead small animals, or their feces. Together, it is called marine snow because the flakes look like snow as they sink through the water column. There can be hundreds of different bacteria in one flake in addition to particles of organic matter.

"Not much is known about how marine snow responds to the increasing pressure when it sinks. But it is known that marine snow is food for an enormous number of microbes and small animals on the seabed. In fact, there are more microbes in the part of the ocean that lies at or below 1000 meters depth than anywhere else on Earth. This habitat is extremely large, and there can be a long distance between the microbes down there, but nevertheless a huge number of Earth's organisms thrive under high pressure, and we don't know how", says biologist Peter Stief, who is the lead author of the study.

Unconventional Approach to C. Diff

C. difficile bacteria seen through a scanning electron microscope and colored green.
Image Credit: Janice Carr via CDC

Clostridioides difficile (C. diff) intestinal infections can cause severe, debilitating diarrhea in patients who are hospitalized or on immunosuppressive therapies. The infections can be very hard to eradicate, roaring back when patients try to taper their antibiotics. Many people wind up on antibiotics for months and can become resistant to three or more of them.

“Often being on antibiotics isn’t sufficient,” explained Meenakshi Rao, Harvard Medical School assistant professor of pediatrics at Boston Children’s Hospital. “The infection can catalyze severe, runaway inflammation, especially in patients with inflammatory bowel disease.”

This inflammation, in turn, promotes C. diff colonization of intestinal tissue. And antibiotics themselves could be part of the problem.

“Once we attack C. diff with antibiotics, it disrupts the gut microbiome,” said Min Dong, HMS associate professor of surgery at Boston Children’s, whose lab studies bacterial toxins and how to combat them. “That creates an opportunity for severe, recurring infection, and it becomes a vicious cycle.”

Antibiotic resistance can impair subsequent adaptations in bacteria, new Concordia research suggests

Farhan Chowdhury (left) and Brandon Findlay; “Instead of relying on antibiotic cocktails, we can have an alternative where sequential antibiotic therapies are applied. This can lead to better therapies and give patients more time to recover before resistance evolves.”
Photo Credit: Courtesy of Concordia University

Researchers at Concordia’s Department of Biology and Department of Chemistry and Biochemistry have discovered a possible new avenue of treatment that can help slow antibiotic resistance in bacteria.

PhD candidate Farhan Chowdhury and associate professor Brandon Findlay recently shared the results of their research in a recent paper published in the journal ACS Infectious Diseases. The researchers describe how a strain of the bacteria E. coli is left severely weakened after it has developed resistance to the antibiotic chloramphenicol (CHL). This weakness leaves the bacteria unable to adapt to other types of antibiotics.

Understanding the ways in which resistance impairments evolve can help clinicians better target pathogens in patients.

“Instead of relying on antibiotic cocktails, we can have an alternative where sequential antibiotic therapies are applied,” Chowdhury explains.

“Clinicians can select the sequence of medication by seeing if a first antibiotic imposes deficits on the bacteria, which would slow down the evolution of resistance in the subsequent ones. This can lead to better therapies and give patients more time to recover before resistance evolves.”

Scientists discover links between Alzheimer’s disease and gut microbiota

Photo (L-R): Dr Stefanie Grabrucker (a postdoctoral researcher) and Professor Yvonne Nolan, of APC Microbiome Ireland and the Department of Anatomy and Neuroscience.
Photo Credit: Ms Bereniece Riedewald.

Researchers have discovered the link between gut microbiota and Alzheimer’s disease.

For the first time, researchers have found that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming its role in the disease.

The research was led by Professor Yvonne Nolan, APC Microbiome Ireland, a world leading SFI funded research center based at University College Cork (UCC), and the Department of Anatomy and Neuroscience, UCC, with Professor Sandrine Thuret at King’s College London and Dr Annamaria Cattaneo IRCCS Fatebenefratelli, Italy. The study supports the emergence of the gut microbiome as a key target for investigation in Alzheimer’s disease due to its particular susceptibility to lifestyle and environmental influences.

Published in Brain, the study shows that memory impairments in people with Alzheimer’s could be transferred to young animals through transplant of gut microbiota. Alzheimer’s patients had a higher abundance of inflammation-promoting bacteria in fecal samples, and these changes were directly associated with their cognitive status.