Fungal pathogenesis is a significant medical problem. Fungi infect humans, plants and animals; because of their eukaryotic nature, it has been difficult to develop novel antifungal drugs which are not toxic to the host. It would be desirable to establish a model host-fungal pathogen system in order to identify virulence genes in the pathogen and immune response genes in the host. Although several fungal species have been shown to infect C. elegans, none of them is a well-characterized genetic model organism. On that basis we studied interaction between C. elegans as host and the yeast S. cerevisiae as pathogen. On mixed lawns of E. coli and S. cerevisiae, adult wild-type C. elegans showed a tail swelling similar to the deformed anal region (Dar) phenotype described for infection by the bacterium M. nematophilum. This phenotype is not induced by heat-killed yeast, and can be reversed by transferring worms to non-yeast containing plates. As proof of concept we have shown that yeast strains carrying a deletion in gene
yap1 fail to induce the Dar phenotype. Yap1 encodes a fungal-specific transcription factor that has been implicated in pathogenesis by indirect evidence. YAP1 has two distinct functions: mediating responses to oxidative stress as well as pleiotropic drug resistance. To investigate which of these is important for producing the Dar phenotype, we tested a yeast strain carrying a deletion in the
sod1 superoxide dismutase gene. Like
yap1, the
sod-1 mutant did not produce the Dar phenotype. In contrast, yeast mutants
pdr1 and
pdr15, which are involved in pleiotropic drug resistance, and
osr5, which is involved in osmotic stress, produced a Dar phenotype similar to wild type, suggesting that the ability to respond to oxidative stress is specifically required for yeast to induce the Dar phenotype. Our working hypothesis is that worms produce reactive oxygen species (ROS) which yeast must counteract in order to be able to induce the Dar phenotype. We are currently testing candidate C. elegans mutants for increased sensitivity or resistance to Dar induction by yeast.