Transcriptomics

Dataset Information

185

Genome-wide expression and location analyses of the Candida albicans Tac1p regulon


ABSTRACT: A major mechanism of azole resistance in Candida albicans is the over-expression of the genes encoding the ABC transporters Cdr1p and Cdr2p. Constitutive over-expression of these efflux pumps is due to mutations in the gene encoding Tac1p, resulting in hyperactivity of this zinc cluster transcription factor. In order to identify the transcriptional targets of Tac1p, we examined four matched sets of clinical isolates representing the development of CDR1- and CDR2-mediated azole resistance, using gene expression profiling analysis. We identified 31 genes that were consistently up-regulated with CDR1 and CDR2, including TAC1 itself, as well as 12 consistently down-regulated genes. When a resistant strain deleted for TAC1 was similarly examined, the expression of almost all of these genes was returned to levels similar to those in the matched azole-susceptible isolate. Keywords: gene expression profiling Four clinical match isolates (azole susceptible and resistant) were grown as three independent replicates for each set to mid-log phase. A TAC1 knockout derived from resistant isolate 5674 was also grown as three independent replicates. Each resistant isolate was compared to its susceptible parent, and the TAC1 knockout was compared to the susceptible parent (5457) of the resistant isolate, 5674.

ORGANISM(S): Candida albicans  

SUBMITTER: David Rogers   Lijing Xu  Saloua Saidane  Kathy S Barker  Katherine S Barker  Ramin Homayouni  Sadri Znaidi  Teresa T Liu  Andre Nantel  Joachim Morschhauser  Martine Raymond 

PROVIDER: E-GEOD-8727 | ArrayExpress | 2010-05-25

SECONDARY ACCESSION(S): GSE8727PRJNA101981

REPOSITORIES: GEO, ArrayExpress

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Publications

The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans.

Morschhäuser Joachim J   Barker Katherine S KS   Liu Teresa T TT   BlaB-Warmuth Julia J   Homayouni Ramin R   Rogers P David PD  

PLoS pathogens 20071101 11


Constitutive overexpression of the MDR1 (multidrug resistance) gene, which encodes a multidrug efflux pump of the major facilitator superfamily, is a frequent cause of resistance to fluconazole and other toxic compounds in clinical Candida albicans strains, but the mechanism of MDR1 upregulation has not been resolved. By genome-wide gene expression analysis we have identified a zinc cluster transcription factor, designated as MRR1 (multidrug resistance regulator), that was coordinately upregulat  ...[more]

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