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.
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 sod1Delta and yap1Delta, 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.
Jain
Charu
C
Department of Biology and Biotechnology, Life Sciences and Bioengineering Center at Gateway Park, Worcester Polytechnic Institute, MA 01605, USA.
Yun
Meijiang
M
Politz
Samuel M
SM
Rao
Reeta Prusty
RP
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D006801:Humans; D009154:Mutation; D009181:Mycoses / Q000382:microbiology*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; C544706:Bli-3 protein, C elegans; D010088:Oxidoreductases