Molly Bletz, assistant professor of disease ecology at Penn State, has been awarded a 2025 New Investigator Grant by the Charles E. Kaufman Foundation, which is administered by The Pittsburgh Foundation and awards grants to support scientists at Pennsylvania colleges and universities conducting innovative and interdisciplinary research. The grant, one of four awarded across the commonwealth fthis year and about $150,000, will fund a project investigating what Bletz calls the "infectome," a new framework for understanding disease. Her proposal goes beyond specific disease-causing pathogens and instead widens the scope to examining the complex interactions between fungal pathogens and the existing microbial ecosystem in the body.
"A lot of times we study things just by themselves," Bletz said. "We study one organism, one pathogen and one host. Increasingly, we're aware that microbiomes are these complex communities, and so it's not just about the one-to-one interaction of a host to a pathogen but this whole high-dimensional space of microbial interactions."
Bletz's background is in disease ecology and she studies amphibian models. Some of the pathogens in those models, like the fungus Batrachochytrium, produce small molecules that inhibit the host's immune response. Bletz's inquiry concerns the other microbes in the host and their roles in blunting the pathogen's attack.
"With this new project, I'm interested in understanding how the host's microbiome might intercept molecules produced by a pathogen," Bletz said. "What if host microbes disarm fungal pathogens not only by limiting growth, but dampening or metabolizing their secreted virulence factors?"
Those microbes could incorporate the compounds into their own metabolism, consume and break them down, or chemically transform them into different molecules that no longer affect the host, Bletz said. Such processes could reduce or neutralize pathogen virulence, altering how infection unfolds and demonstrating how microbial community dynamics may play an active role in modulating disease.
"We know microbes can influence the virulence factors of pathogens," she said. "A Streptococcus species will limit hyphal formation, which is a virulence factor for Candida, the fungus that causes yeast infection in humans. An exciting aspect of our new project is to think about the whole community of interactions together in an understudied model amphibian system."
The Kaufman grant will support Bletz's initial research, but she said she sees potential for translational science to eventually create treatments that rely on deeper understandings of the infectome.
"A cocktail of key microbes could act against problematic compounds," she said. "If we decode these mechanisms of microbiome-mediated effects on immunity, we can develop tools that could reduce the virulence of fungal pathogens. We can discover different ways and more creative ways for managing fungal disease, which is a problem for human health, for biodiversity, and for food security."
The project will utilize multiple resources available at the Huck Institutes of the Life Sciences, with the Genomics Core Facility employed to build in silico models of the microbial communities and the Metabolomics Core Facility tasked with monitoring the metabolites produced. Also involved will be Bletz Lab member Talon Jost, a student in the ecology graduate program who is pursuing a dual title in microbiome sciences offered by Huck's One Health Microbiome Center and also a trainee with the Biotechnological & Integrative Opportunities in Microbiome Sciences T32 training grant.
