Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Antimicrob Agents Chemother. 2000 May;44(5):1255-65.

Genome-wide expression patterns in Saccharomyces cerevisiae: comparison of drug treatments and genetic alterations affecting biosynthesis of ergosterol.

Author information

  • 1Pharmacia & Upjohn, Kalamazoo, Michigan 49001, USA.

Abstract

Enzymes in the ergosterol-biosynthetic pathway are the targets of a number of antifungal agents including azoles, allylamines, and morpholines. In order to understand the response of Saccharomyces cerevisiae to perturbations in the ergosterol pathway, genome-wide transcript profiles following exposure to a number of antifungal agents targeting ergosterol biosynthesis (clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole, terbinafine, and amorolfine) were obtained. These profiles were compared to the transcript profiles of strains containing deletions of one of the late-stage ergosterol genes: ERG2, ERG5, or ERG6. A total of 234 genes were identified as responsive, including the majority of genes from the ergosterol pathway. Expression of several responsive genes, including ERG25, YER067W, and YNL300W, was also monitored by PCR over time following exposure to ketoconazole. The kinetics of transcriptional response support the conditions selected for the microarray experiment. In addition to ergosterol-biosynthetic genes, 36 mitochondrial genes and a number of other genes with roles related to ergosterol function were responsive, as were a number of genes responsive to oxidative stress. Transcriptional changes related to heme biosynthesis were observed in cells treated with chemical agents, suggesting an additional effect of exposure to these compounds. The expression profile in response to a novel imidazole, PNU-144248E, was also determined. The concordance of responsive genes suggests that this compound has the same mode of action as other azoles. Thus, genome-wide transcript profiles can be used to predict the mode of action of a chemical agent as well as to characterize expression changes in response to perturbation of a metabolic pathway.

PMID:
10770760
[PubMed - indexed for MEDLINE]
PMCID:
PMC89853
Free PMC Article

Images from this publication.See all images (5)Free text

FIG. 1
FIG. 2
FIG. 3
FIG. 4
FIG. 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk