CAREER: Microbiome regulation by amphibian skin peptides

Microbes, including bacteria and fungi, are in constant interaction with the immune system. Little is known about how this relationship helps prevent disease. Thus host-microbe biology is an exciting frontier for discovery. Amphibians are an excellent model system to study the symbiotic relationships between animal hosts and microbes because their moist skin surfaces have properties similar to the human digestive tract and lungs. The current award will use this model to test whether peptides secreted onto the skin of the northern leopard frog regulate skin microbiota by supporting the growth of beneficial bacteria and by inhibiting the growth of pathogenic bacteria. The results of this study will inform microbial therapies and contribute to conservation efforts as well. Since one third of the world's amphibian species are currently threatened, this research will also inform amphibian disease management and conservation at a critical time when continued disease emergence is harming biodiversity. Central to the NSF CAREER award, this project integrates research with education by implementing a Mentored Research Lab course on Microbiome and Disease Ecology to provide authentic research experiences. In learning communities, graduate students and postdoctoral researchers will give mentorship to undergraduates. An advisory board of microbial and disease ecologists, professional education specialists, and faculty will provide collaboration and training. The project will target recruitment from underrepresented groups at all levels. In this collaborative setting, students will be encouraged to design experiments on the cutting edge of host-microbe biology.<br/> <br/>Emerging infectious diseases threaten wildlife populations. Chytridiomycosis is one example of an emerging infectious disease of amphibians, such as leopard frogs, and is caused by the fungus Batrachochytrium dendrobatidis. This project will describe key interactions of host peptides and symbiotic microbes for defending the host against fungal infections and identify a novel mechanism of microbiome regulation by skin defense peptides. The central hypothesis is that amphibian skin peptides regulate the skin microbiome, thus impacting host-pathogen interactions. Specific objectives are: (1) Identify interactions between skin defense peptides and microbiota under field and controlled mesocosm conditions including comparisons among host life-history stages with different peptide expression patterns, (2) test if host skin peptides support microbes isolated from hosts (promicrobial function) and inhibit potentially invasive environmental microbes (antimicrobial function), (3) examine the role of defense peptides in regulating microbiome stability by experimentally reducing skin peptides and testing for microbial dysbiosis under different environmental conditions, and (4) test the role of microbial community phylogenetic diversity prompting complexity of host defense peptide expression on the skin through controlled experiments. Determining the trajectory of the microbiota through time under different environmental conditions will provide insight on whether microbiome assembly is stochastic, resilient, or adaptively shifts as defense peptides regenerate.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.