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| Status |
Public on Mar 11, 2013 |
| Title |
The Candida glabrata transcription factor Stb5p is a negative regulator of ATP-binding cassette transporters |
| Platform organisms |
Nakaseomyces glabratus; Nakaseomyces glabratus CBS 138 |
| Sample organism |
Nakaseomyces glabratus |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
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| Overall design |
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.
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| Citation(s) |
23229483 |
| |
| Submission date |
Apr 05, 2012 |
| Last update date |
Mar 11, 2013 |
| Contact name |
Jason A Noble |
| E-mail(s) |
noblej2@mail.nih.gov
|
| Phone |
301-4968956
|
| Organization name |
National Institutes of Health
|
| Department |
NIAID
|
| Lab |
Clinical Mycology
|
| Street address |
10 Center Drive, Building 10, Room 11N228
|
| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL8174 |
NIAID Cgaa -- Candida glabrata 6K |
| GPL10325 |
NIAID Cgda -- Candida glabrata 6K - mAdb version |
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| Samples (13)
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| GSM910261 |
Cgstb5D - repeat 4 - reverse fluoro - mAdbID:112368 |
| GSM910262 |
CgSTB5OE - repeat 1 - mAdbID:112908 |
| GSM910263 |
CgSTB5OE - repeat 2 - mAdbID:112909 |
| GSM910264 |
CgSTB5OE - repeat 3 - mAdbID:112910 |
| GSM910265 |
CgSTB5OE - repeat 4 - reverse fluoro - mAdbID:112911 |
| GSM910266 |
CgPDR1OE - repeat 1 - mAdbID:56651 |
| GSM910267 |
CgPDR1OE - repeat 2 - mAdbID:56654 |
| GSM910268 |
CgPDR1OE - repeat 3 - mAdbID:56814 |
| GSM910269 |
CgPDR1OE - repeat 4 - mAdbID:56815 |
| GSM910270 |
CgPDR1OE - repeat 5 - reverse fluoro - mAdbID:56816 |
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| Relations |
| BioProject |
PRJNA158089 |
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