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PMID: 11606528 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

Genetics ·Vol. 159 ·No. 2 ·2001-10-00 ·Pages 499-513

Goldstein AL, McCusker JH

Abstract

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.

MeSH Terms
Amino Acids/biosynthesis Animals Base Sequence DNA Primers Drug Resistance, Microbial Fungal Proteins/genetics,physiology Male Mice Mitochondria/genetics Molecular Sequence Data Mycoses/microbiology Nucleotides/biosynthesis Saccharomyces cerevisiae/drug effects,genetics,pathogenicity,physiology
Chemicals
Amino Acids DNA Primers Fungal Proteins Nucleotides
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Goldstein A L
Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
McCusker J H
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/159.2.499
Published
2001-10-00
Pages
499-513
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1461844
Subset
IM
Grants
NIAID NIH HHS · P01-AI44975 · United States
NIGMS NIH HHS · R01-GM58476 · United States
NIAID NIH HHS · T32-AI07392 · United States
NCI NIH HHS · T32-CA09111 · United States
External Links
PubMed source DOI: 10.1093/genetics/159.2.499 PMC Full Text View journal details
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