ROX1 and ERG regulation in Saccharomyces cerevisiae: implications for antifungal susceptibility.
Yeasts respond to treatment with azoles and other sterol biosynthesis inhibitors by upregulating the expression of the ERG genes responsible for ergosterol production. Previous studies on Saccharomyces cerevisiae implicated the ROX1 repressor in ERG regulation. We report that ROX1 deletion resulted in 2.5- to 16-fold-lower susceptibilities to azoles and terbinafine. In untreated cultures, ERG11 was maximally expressed in mid-log phase and expression decreased in late log phase, while the inverse was observed for ROX1. In azole-treated cultures, ERG11 upregulation was preceded by a decrease in ROX1 RNA. These inverse correlations suggest that transcriptional regulation of ROX1 is an important determinant of ERG expression and hence of azole and terbinafine susceptibilities.
Henry
Karl W
KW
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Nickels
Joseph T
JT
Edlind
Thomas D
TD
D000935:Antifungal Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004875:Ergosterol / Q000096:biosynthesis* / Q000235:genetics; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D009281:Naphthalenes / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D000077291:Terbinafine; D013997:Time Factors; D015854:Up-Regulation
D000935:Antifungal Agents; D004268:DNA-Binding Proteins; D009281:Naphthalenes; C083348:ROX1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D000077291:Terbinafine; D004875:Ergosterol