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Genome-wide expression profiling of experimentally induced azole resistance in Saccharomyces cerevisiae


, : Genome-wide expression profiling of experimentally induced azole resistance in Saccharomyces cerevisiae. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 42: 377

Background: This study was performed to identify genes that are differentially expressed in experimentally induced azole resistance in S. cerevisiae that might contribute to this process. Methods: Resistant isolates generated by serially passing S. cerevisiae ATCC strain 9763 in increasing concentrations of fluconazole (FCZ) (isolate 9763F) or itraconazole (ITZ) (isolate 9763I) were grown to early exponential phase in YPD for RNA isolation. Microarray hybridization was performed in duplicate using the Affymetrix Yeast S98 Array. Changes in expression of gtoreq2 fold were considered differentially expressed. Results: The MICs for FCZ were 16 mug/mL for 9763 and gtoreq64 mug/mL for 9763F and 9763I, while the MICs for ITZ were 2 mug/mL for 9763 and gtoreq16 mu/mL for 9763F and 9763I. A total of 113 and 120 genes were found to be differentially expressed in 9763F and 9763I, respectively, as compared to 9763. For 9763F these included up-regulation of RAD54, and down-regulation of genes involved in cell wall maintenance (CWP1, FKS1, GFA1, TIR1, TIR3), lipid, fatty-acid and sterol metabolism (FAS1, FAS2, ERG5, ERG13), and protein folding (HSC82, HSP30, SSA1, SSA2). For 9763I these included up-regulation of genes involved in cell stress (CUP1), cell wall maintenance (CCW12, TIR4), and small molecule transport (AUS1, YHR048W), and downregulation of genes involved in cell wall maintenance (FLO5, FLO9), energy generation (ATP2, ATP9, COX4, COX5A, COX6, COX7, COX8, COX12, QCR2, QCR8, QCR9, QCR10), lipid, fatty-acid and sterol metabolism (OPI3, CHO1, HMG1, ERG8, ERG13), protein folding (HSP60, SSA1, SSA2), and small molecule transport (FRE1, FRE2, TPO1, FET3). A total of 27 genes were commonly differentially expressed in both 9763F and 9763I as compared to 9763. Conclusion: Coordinate changes in the expression of sets of genes involved in these cellular functions in association with azole resistance are suggestive of novel mechanisms for this process.

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