Latest news with #C.neoformans
Yahoo
10-06-2025
- Health
- Yahoo
New research reveals a deadly fungal pathogen's vulnerabilities
The study from the Stowers Institute and the University of Georgia uncovers more than 300 potential targets for drug development for a lethal fungus. KANSAS CITY, Mo., June 10, 2025 /PRNewswire/ -- Fungal infections, particularly in immunocompromised individuals, are responsible for nearly four million deaths annually—however, current treatments are limited and are frequently ineffective. Now, scientists at the Stowers Institute for Medical Research and the University of Georgia discover how the lethal pathogenic fungus, Cryptococcus neoformans, thrives, allowing them to identify potential novel therapeutic targets for treatment. Published in PLoS BIOLOGY on June 5, 2025, the study refined a genetic tool to identify which genes in C. neoformans are essential for its survival. Importantly, the research team uncovered more than 1,400 required genes, including more than 300 that share no similarity with human genes, making them promising targets for new antifungal drugs with reduced risks for side effects. "Cryptococcus neoformans kills around 150,000 people a year. It's the AIDS-defining illness in the majority of HIV patients. Current treatments are limited, and outcomes are often poor," said lead author Blake Billmyre, Ph.D., Assistant Professor at the University of Georgia and former postdoctoral researcher in the lab of Stowers Associate Investigator SaraH Zanders, Ph.D. "There is an urgent need to develop new therapies, and this study provides an atlas." Although humans and fungi bear little resemblance, genetically, we are surprisingly similar, which has historically made antifungal drug development difficult. Identifying essential genes in fungal pathogens that have no analog to human genes is critical for pinpointing potential antifungal agents that do not harm human cells. The team uncovered 302 ideal therapeutic targets in C. neoformans—however, because drug development is costly, the researchers also identified a subset of around 30 essential genes conserved across many pathogenic fungi, or 30 potential therapies that could destroy most fungal invaders. "A big question in biology is which genes are essential for life as well as how they might change over evolutionary time," said Zanders. "Blake's TN-seq project opens the door to genome-wide screens for important traits in pathogenic fungi and will speed the pace of drug discovery." The team used a genetic technique called transposon mutagenesis sequencing, or TN-seq, where they damaged C. neoformans' genome by bombarding millions of cells with small DNA segments called transposons. "The analogy we use to explain TN-seq dates back to WWII," said Billmyre. "Fighter planes returning to hangars were mapped for bullet damage to devise ways to strengthen them. However, areas of planes lacking damage were not necessarily better reinforced, but rather were never mapped because they never returned, a phenomenon called survivorship bias." Transposons landing within essential genes cause the fungal cells to die. By sequencing the DNA of the surviving cells, researchers can map which genes are vital for survival and which are not. Zanders explained: "The TN-seq approach mirrors this survivorship bias with transposon-ridden fungi. When we look genome-wide at all the places with and without damage, we can infer that if you damage a required region of the genome, the organism will die." TN-seq has been used widely in bacteria and in more established fungal species like baker's yeast. This is the first time the approach was adapted for C. neoformans. It allowed the team to create a mutant library for C. neoformans—with millions of transposon-induced mutations including those in DNA that regulate essential genes. The researchers could then ask even more nuanced questions, such as which genes contribute not only to survival but also to resistance of antifungal drugs. "Traditional methods involve deleting one gene at a time, but TN-seq lets us make deletions for the entire genome, allowing us to rapidly identify the repertoire of essential genes in Cryptococcus," said Billmyre. "In addition, we were also able to use the tool to test both essential and non-essential genes that confer resistance to the most common antifungal, fluconazole." Billmyre was recently awarded the prestigious NIH New Innovator Award to examine how fungi evolve to grow at high temperatures, which is key to understanding pathogenicity. "My lab is now trying to understand the network of genes that enable fungal pathogens to grow at human body temperature," said Billmyre. "This can inform us of what might happen in the future if increases in global temperature cause different species of fungi to acquire pathogenic properties." Additional authors include Caroline Craig, Joshua Lyon, Claire Reichardt, Amy Kuhn, and Michael Eickbush. This work was funded by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) (awards: DP2GM132936, R35GM151982), the National Institute of Allergy and Infectious Diseases of the NIH (award: DP2AI184725), and with institutional support from the University of Georgia and the Stowers Institute for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. About the Stowers Institute for Medical Research Founded in 1994 through the generosity of Jim Stowers, founder of American Century Investments, and his wife, Virginia, the Stowers Institute for Medical Research is a non-profit, biomedical research organization with a focus on foundational research. Its mission is to expand our understanding of the secrets of life and improve life's quality through innovative approaches to the causes, treatment, and prevention of diseases. The Institute consists of 20 independent research programs. Of the approximately 500 members, over 370 are scientific staff that include principal investigators, technology center directors, postdoctoral scientists, graduate students, and technical support staff. Learn more about the Institute at and about its graduate program at Media Contact: Joe Chiodo, Head of External Communications and Media Relations 724.462.8529 press@ View original content to download multimedia: SOURCE Stowers Institute for Medical Research
Yahoo
04-06-2025
- General
- Yahoo
Watch bacteria ‘hitchhike' and zoom around
The tiny world of microorganisms is full of microbes competing in a major life or death battle. The tiny lifeforms compete for turf, gobble up some pollutants, spew chemicals at their foes, and will exploit terrain in order to get an edge and thrive. New research into this microscopic turf war found that bacteria can speed up by using fluid pockets that are shaped by nearby yeast cells. Hitching a ride with these moisture trails allows the bacteria to spread faster and swim further. The findings are detailed in a study published June 4 in the Cell Press journal Biophysical Journal and reveal a new way that microbes travel through plants, soil, and even our own bodies. 'When studying microbial interactions, research often focuses on the chemical nature of these interactions,' study co-author and Cornell University microbiome engineer Divakar Badal said in a statement. 'But we learned that physical properties also play an important role in how microbes grow and spread.' In the study, the team focused on the bacterium Pseudomonas aeruginosa and fungus Cryptococcus neoformans. P. aeruginosa is a rod-shaped bacteria found in soil and human airways and has tail-like propellers. According to the Centers for Disease Control and Prevention, it can cause infections in the blood, lungs (pneumonia), urinary tract, or other parts of the body after surgery. C. neoformans is a stationary yeast that can be deadly in those with weakened immune systems and lives throughout the world. Infections from this fungus can affect the different parts of the body, but causes lung or brain infections (cryptococcal meningitis) most often. The team watched under a microscope as the two species closed in on each other. The P. aeruginosa bacterium eventually swarmed into the puddle-like fluid surrounding the C. neoformans yeast. The bacteria cultured with yeast spread up to 14.5 times faster than when it was cultured alone. Additionally, isolated bacterial colonies quickly connected into continuous clumps. At a microscopic scale, P. aeruginosa is comparable to a grain of rice. On that same scale, the yeast is about the size of a grape. These larger yeast bodies draw in moisture from the surface, which forms a thin halo of fluid that acts as a temporary swimming lane. This lane allows the bacteria to bypass the usual physical limits of a dry surface. When the team replaced the live yeast with dead ones or glass beads, the same halo effect was produced, indicating that the puddles were driving it. 'The bigger the obstacle, yeast and glass beads alike, the more fluid you have around it, and it's better for Pseudomonas,' added Varsha Singh, a study co-author and molecular biologist at the University of Dundee in Scotland. 'So, it's leveraging what could have been an obstacle to move farther ahead.' [ Related: Bacteria wars are raging in soil, and it's keeping ecosystems healthy. ] The team also found that the spread of the bacteria ebbs and flows within the landscape that the growing yeast cells create. They built a model to simulate the interactions between both the bacterium and yeast to better understand the dynamics at play. The model indicates that faster-growing yeast species like C. albicans altered the fluid landscape more dramatically, affecting just how quickly bacteria could travel. 'I was absolutely blown away by how well our model predictions match the experimental results,' said Danny Raj M, a study co-author and engineer at the Indian Institute of Technology Madras. 'In a sense, the model is a virtual lab that simulates real behaviors. By changing the parameters, from growth rates to humidity, we can answer a number of questions.' According to the team, the implications of this research go beyond the model and lab. Bacteria and yeast coexist in plants, soil, water, and the human body. The ability to ride fluid films may be one of the factors that helps bacteria colonize these environments more effectively, especially if moisture is scarce. The team plans to examine the way that both species interact in the real world to learn more. 'We tend to think of microbiology in an anthropomorphic way, focused on human lungs or the gut because we can relate to them,' said Singh. 'But much of it plays out in the soil and other environments. That gives us a wonderful opportunity to explore new questions. I think that's where the next frontier is.'
Yahoo
03-06-2025
- General
- Yahoo
Cannabis Compound Could Protect Us From Deadly Fungal Disease
A dangerous fungal pathogen has proven no match for what may be one of the most useful plants in nature. Scientists studying the chemical properties of cannabis have found it kills one of the most dangerous fungal pathogens in the world – in a laboratory setting, at least. Cryptococcus neoformans, a species of fungus behind cryptococcosis and cryptococcal meningitis, appears to be vulnerable to topical treatment with cannabidiol and cannabidivarin, compounds found in the plant Cannabis sativa. "When Cryptococcus neoformans gets to your central nervous system, it causes life-threatening meningitis," explains biologist Hue Dinh of Macquarie University in Australia. "The mortality rate is very high, and it's really hard to treat." Fungal pathogens pose a pretty significant threat to human health, with around 300 species known to cause diseases in humans, with varying levels of severity. Because pathogens such as fungi and bacteria continually develop resistances to drugs, new treatment options are continually needed to keep them at bay. One strategy is to look at medications that have already been approved for human use for other ailments. Dinh and her colleagues turned their research to cannabis, isolating five compounds to test on C. neoformans and a range of other pathogens. They isolated the fungal species in a lab, and applied the compounds. Cannabidiol (CBD), which is non-psychoactive, and cannabidivarin (CBDV), which is psychoactive, both killed C. neoformans adroitly, acting even faster than current antifungal treatments. They were also effective at eradicating the fungal pathogens responsible for such conditions as jock itch and athlete's foot. "Proteomics analysis revealed that the antifungal activity of CBD and CBDV was linked to destabilization of the membrane, alterations in ergosterol biosynthesis, disruption of metabolic pathways, as well as selective involvement of mitochondrial-associated proteins," the researchers wrote in their paper. It's one thing to kill a fungus in a petri dish, but quite another to observe the treatment working in a living system. To test their findings further, the researchers turned to Galleria mellonella, the greater wax moth. The larvae of this moth possess an innate immune response that is similar to that of mammals. They are also inexpensive to obtain, have short lifespans, and require no special equipment to keep, making them an excellent model for large-scale studies of infectious pathogens and the treatments thereof. Moth larvae were given small burn wounds, and then divided into groups. One group was left alone with just the burn wounds as a control; the remainder were infected with C. neoformans, and treated with different medicaments. One group was treated with CBD dissolved in dimethyl sulfide. Another group was treated with dimethyl sulfide without the CBD. Finally, the last group was treated using Amphotericin B, a medication used to treat serious fungal infections in humans. The results were striking. The survival rate of the larvae treated with CBD was significantly higher than the survival rate of the larvae treated with the dimethyl sulfide alone, and also higher than the survival rate of the Amphotericin B group. In fact, it was nearly as high as the survival rate of the control group – the larvae that had not been infected with the fungus at all. Although the treatment of infections that reach the lungs and brain is a bit more complicated, the result suggests that, at the very least, the topical application of cannabidiol might be effective at treating a range of fungal skin infections. "If we can demonstrate that these ones work well for common infections," Dinh says, "you could actually just get some CBD oil and then rub it on your skin to treat it." The research has been published in PLOS Neglected Tropical Diseases. Pooping Is a High-Stakes Event That Could Be Fatal For One Group Misophonia Has Genetic Links to Depression And Anxiety, Study Finds Experimental Drug Helped Cancer Patients Live 40% Longer in Clinical Trial
