Unknown,Transcriptomics,Genomics,Proteomics

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The Candida glabrata transcription factor Stb5p is a negative regulator of ATP-binding cassette transporters

ABSTRACT: The opportunistic yeast pathogen Candida glabrata is recognized for its ability to acquire resistance during prolonged treatment with azole antifungals. Resistance to azoles is largely mediated by the transcription factor PDR1, resulting in the upregulation of ATP-binding cassette (ABC) transporter proteins and drug efflux. Studies in the related yeast Saccharomyces cerevisiae have shown Pdr1p forms a heterodimer with another transcription factor, Stb5p. In C. glabrata the ORF designated CAGL0I02552g has 38.8% amino acid identity with STB5 (YHR178w), and shares an N-terminal Zn2Cys6 binuclear cluster domain and a fungal specific transcriptional factor domain, prompting us to test for homologous function and a possible role in azole resistance. Complementation of deltayhr178w (stb5) with CAGL0I02552g resolved the increased sensitivity to cold, hydrogen peroxide and caffeine of the mutant, for which reason we designated CAGl0I02552g as CgSTB5. Overexpression of CgSTB5 in C. glabrata repressed azole resistance, whereas deletion of CgSTB5 increased resistance, both by a mechanism independent of CgPDR1. Expression analysis found that CgSTB5 shares many of the same transcriptional targets as CgPDR1 but, unlike the later, is a negative regulator of pleiotropic drug resistance, including the ABC transporter genes CDR1,PDH1, and YOR1. The CgPDR1OE (n=5) arrays consisted of five technical repeats with one prepared using reciprocal labeling. The Cgstb5delta (n=4) and CgSTB5OE (n=4) arrays consisted of four technical repeats each with one prepared using reciprocal labeling.

ORGANISM(S): Candida glabrata

SUBMITTER: Jason Noble

PROVIDER: E-GEOD-37071 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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STB5 is a negative regulator of azole resistance in Candida glabrata.

Noble Jason A JA Tsai Huei-Fung HF Suffis Sara D SD Su Qin Q Myers Timothy G TG Bennett John E JE

Antimicrobial agents and chemotherapy 20121210 2

The opportunistic yeast pathogen Candida glabrata is recognized for its ability to acquire resistance during prolonged treatment with azole antifungals (J. E. Bennett, K. Izumikawa, and K. A. Marr. Antimicrob. Agents Chemother. 48:1773-1777, 2004). Resistance to azoles is largely mediated by the transcription factor PDR1, resulting in the upregulation of ATP-binding cassette (ABC) transporter proteins and drug efflux. Studies in the related yeast Saccharomyces cerevisiae have shown that Pdr1p fo ...[more]

PMID: 23229483

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