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Eukaryotic Cell, August 2009, p. 1218-1227, Vol. 8, No. 8
1535-9778/09/$08.00+0     doi:10.1128/EC.00367-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Pathogenesis Assay Using Saccharomyces cerevisiae and Caenorhabditis elegans Reveals Novel Roles for Yeast AP-1, Yap1, and Host Dual Oxidase BLI-3 in Fungal Pathogenesis{triangledown}

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, Massachusetts 01605

Received 14 November 2008/ Accepted 29 May 2009

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 pathogenesis assay using Caenorhabditis elegans, an established model host, with 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{Delta} and yap1{Delta}, which cannot withstand ROS, fail to cause disease, except in bli-3 worms, which carry a mutation in a dual oxidase gene. Chemical inhibition of the NADPH oxidase activity abolishes ROS production in worms exposed to yeast. This pathogenesis 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.

* Corresponding author. Mailing address: Department of Biology and Biotechnology, Life Sciences and Bioengineering Center at Gateway Park, Worcester Polytechnic Institute, Worcester, MA 01605. Phone: (508) 831-6120. Fax: (508) 831-5936. E-mail: rpr{at}wpi.edu

{triangledown} Published ahead of print on 5 June 2009.

Eukaryotic Cell, August 2009, p. 1218-1227, Vol. 8, No. 8
1535-9778/09/$08.00+0     doi:10.1128/EC.00367-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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