Development of Saccharomyces cerevisae as a model pathogen: A system for the genetic identification of gene products required for survival in the mammalian host environment

Saccharomyces cerevisiae, a close relative of the pathogenic Candida specie s, is an emerging opportunistic pathogen. An isogenic series of S. cerevisi ae strains, derived from a human clinical isolate, were used to examine the role of evolutionarily conserved pathways in fungal survival in a mouse ho st. As is the case for the corresponding Candida albicans and Cryptococcus neoformans mutants, S. cerevisiae purine and pyrimidine auxotrophs were sev erely deficient in survival, consistent with there being evolutionary conse rvation of survival traits. Resistance to the antifungal drug 5-fluorocytos ine was not deleterious and appeared to be slightly advantageous in vivo. O f mutants in three amino acid biosynthetic pathways, only leu2 mutants were severely deficient in vivo. Unlike the glyoxylate cycle, respiration was v ery important for survival; however, the mitochondrial genome made a respir ation-independent contribution to survival. Mutants deficient in pseudohyph al formation were tested in vivo; flo11 Delta mutants were phenotypically n eutral while flo8 Delta, tec1 Delta, and flo8 Delta tec1 Delta mutants were slightly deficient. Because of its ease of genetic manipulation and the im mense S. cerevisiae database, which includes the best annotated eukaryotic genome sequence, S. cerevisiae is a superb model system for the identificat ion of gene products important for fungal survival in the mammalian host en vironment.