EC Accepts, published online ahead of print on 5 June 2009

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Eukaryotic Cell doi:10.1128/EC.00367-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A Patho-assay using S. cerevisiae and C. elegans Reveals Novel Roles for Yeast AP-1, Yap1 and Host Dual Oxidase, BLI-3 in Fungal Pathogenesis

Charu Jain, Meijiang Yun, Samuel M. Politz, and Reeta Prusty Rao^*

Department of Biology and Biotechnology, Life Sciences and Bioengineering Center at Gateway Park, Worcester Polytechnic Institute, Worcester, MA 01605, USA

^* To whom correspondence should be addressed. Email: rpr{at}wpi.edu.

Treatment of systemic fungal infections is difficult because of the limited number of antimycotic drugs available. Thus, there is an immediate need for simple and innovative systems to assay the contribution of individual genes to fungal pathogenesis. We have developed a patho-assay using Caenorhabditis elegans, an established model host and Saccharomyces cerevisiae as the invading fungus. We have found that yeast infects nematodes causing disease and death. Our data indicate that the host produces reactive oxygen species (ROS) in response to fungal infection. Yeast mutants sod1 and yap1, which cannot withstand ROS, fail to cause disease, except in bli-3 worms that carry a mutation in a dual oxidase gene. Chemical inhibition of the NADPH oxidase activity abolishes ROS production in worms exposed to yeast. This patho-assay is useful for conducting systematic, whole-genome screens to identify fungal virulence factors as alternative targets for drug development and exploration of host responses to fungal infections.