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

Publication ,  Journal Article
Goldstein, AL; McCusker, JH
Published in: Genetics
October 2001

Saccharomyces cerevisiae, a close relative of the pathogenic Candida species, is an emerging opportunistic pathogen. An isogenic series of S. cerevisiae strains, derived from a human clinical isolate, were used to examine the role of evolutionarily conserved pathways in fungal survival in a mouse host. As is the case for the corresponding Candida albicans and Cryptococcus neoformans mutants, S. cerevisiae purine and pyrimidine auxotrophs were severely deficient in survival, consistent with there being evolutionary conservation of survival traits. Resistance to the antifungal drug 5-fluorocytosine was not deleterious and appeared to be slightly advantageous in vivo. Of mutants in three amino acid biosynthetic pathways, only leu2 mutants were severely deficient in vivo. Unlike the glyoxylate cycle, respiration was very important for survival; however, the mitochondrial genome made a respiration-independent contribution to survival. Mutants deficient in pseudohyphal formation were tested in vivo; flo11Delta mutants were phenotypically neutral while flo8Delta, tec1Delta, and flo8Delta tec1Delta mutants were slightly deficient. Because of its ease of genetic manipulation and the immense S. cerevisiae database, which includes the best annotated eukaryotic genome sequence, S. cerevisiae is a superb model system for the identification of gene products important for fungal survival in the mammalian host environment.

Duke Scholars

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

October 2001

Volume

159

Issue

2

Start / End Page

499 / 513

Location

United States

Related Subject Headings

  • Saccharomyces cerevisiae
  • Nucleotides
  • Mycoses
  • Molecular Sequence Data
  • Mitochondria
  • Mice
  • Male
  • Fungal Proteins
  • Drug Resistance, Microbial
  • Developmental Biology
 

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

October 2001

Volume

159

Issue

2

Start / End Page

499 / 513

Location

United States

Related Subject Headings

  • Saccharomyces cerevisiae
  • Nucleotides
  • Mycoses
  • Molecular Sequence Data
  • Mitochondria
  • Mice
  • Male
  • Fungal Proteins
  • Drug Resistance, Microbial
  • Developmental Biology