BRC-BIO: Multi-omics guided discovery of natural products from the cave and bat microbiome using ecologically inspired synthetic communities

James Madison University, Harrisonburg VA

Investigators

Abstract

As one-fifth of all mammals on Earth, bats play an important role in supporting the health of diverse ecosystems by controlling insect populations, pollinating plants, and harboring unique immune systems that can provide insight into preventing and treating disease. Unfortunately, white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has devastated North American bat populations, killing millions in one of the greatest wildlife disease epidemics in US history. Recent work suggests that bat microbiomes protect their host against WNS but the specific metabolites and environmental triggers for their production have not been identified. By leveraging natural products chemistry, correlative metabolomics, and ecologically inspired synthetic microbial communities, this project aims to understand how bacteria protect against WNS and what metabolites/biosynthetic pathways are responsible for this protection. Results of this study may aid in future conservation efforts and educate the general public about cave microbiology and its impacts on diverse ecosystems. In the near-term, this project will provide opportunities for interdisciplinary research in the PI’s lab and in the form of Course-Based Undergraduate Research Experiences. Building upon the team’s prior work screening bacterial isolates from bat skin microbiome, the team has identified 98 bacterial isolates that inhibit P. destructans in vitro. To lay the scientific foundation for developing probiotic treatments, the PI plans to address the following questions. What metabolites govern host-microbiome-pathogen interactions? How are biosynthetic gene clusters (BGCs) that produce antifungal molecules regulated? How might probiotic treatment of vulnerable bats impact existing communities in treated caves? To address these questions, an interdisciplinary research plan with two Aims is proposed that characterizes the metabolomes of bat-associated bacteria, integrates chemical and genomic data to identify antifungal molecules and their BGCs, and elicits formation of ecologically relevant metabolites from silent BGCs using synthetic communities. Answering these research questions will provide the context for building research capacity of the PI and James Madison University and engaging undergraduate students in interdisciplinary research as part of laboratory-based and course-based activities. 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.