Development and application of innovative tools to mitigate White Nose Syndrome, a lethal fungal disease decimating North American bat populations

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

This project focuses on developing an immune-based strategy to prevent White Nose Syndrome (WNS), a lethal fungal infection of hibernating bats that is spreading across North America. This research will develop a deeper understanding of how the fungal pathogen attacks, and guide management strategies for protecting bats against the devastating impact of WNS. Specifically, the research team will interrogate how a fungal pathogen invades skin through the role of the epidermal growth factor receptor in bats, possibly resulting in a broader understanding of such processes in mammals in general. Additionally, the team will attempt a novel approach of combining vaccination with topical drugs that block infection – with the goals to advance the conservation of several bat species, maintain biodiversity and support ecosystem health. In addition, this project features the training and teaching of early career scientists and wildlife biology trainees and is based on the collaboration of an academic institution and federal agencies – USGS and USFWS. The fundamental research associated with this project is to further understand how the fungus Pseudogymnoascus destructans (Pd for short) initiates infection by adhering to bat skin. It is known that Pd makes contact with keratinocytes (e.g. epithelial cells). This project makes use of a first-of-its-kind keratinocyte cell line from Myotis lucifugus, a bat species that is highly susceptible to WNS. The keratinocyte cell line has provided an ideal model to study how Pd invades bat skin and initiates infection. Preliminary data reveal: (i) the identity of a receptor – epidermal growth factor receptor (EGFR) – that mediates keratinocyte “stealth” invasion by Pd and (ii) the utility of the FDA approved drug gefitinib® that blocks Pd invasion of the cells. Experiments are designed to formally test the role of EGFR in Pd invasion via CRISPR editing of keratinocytes. Because EGFR differs in its structure in susceptible and resistant bats, EGFR from resistant bats will be used to complement the knockout cell line to assess the role of EGFR in explaining WNS susceptibility. Conservation biology is an important aspect of the work. WNS prevention strategies will be implemented in collaboration with the U.S. Geological Survey at the National Wildlife Health Center in partnership with the U.S. Fish and Wildlife Service. Field studies will thus be performed in several U.S. states to investigate the use of gefitinib together with a protective vaccine created by these investigators against Pd infection. This project is being supported via a joint program involving the Divisions of Environmental Biology and Integrative Organismal Systems and the Paul G. Allen Family Foundation. 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.