Henry Karl W, Nickels Joseph T, Edlind Thomas D
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Eukaryot Cell. 2002 Dec;1(6):1041-4. doi: 10.1128/EC.1.6.1041-1044.2002.
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.
酵母通过上调负责麦角甾醇生成的ERG基因的表达来响应唑类和其他甾醇生物合成抑制剂的处理。先前对酿酒酵母的研究表明ROX1阻遏物参与ERG调控。我们报告称,缺失ROX1会导致对唑类和特比萘芬的敏感性降低2.5至16倍。在未处理的培养物中,ERG11在对数中期表达最高,在对数后期表达下降,而ROX1则相反。在唑类处理的培养物中,ERG11上调之前ROX1 RNA会减少。这些负相关表明ROX1的转录调控是ERG表达的重要决定因素,因此也是唑类和特比萘芬敏感性的重要决定因素。