Transcriptomics

Dataset Information

74

Genome-wide expression profile analysis of the Candida glabrata Pdr1 regulon


ABSTRACT: The ABC-transporters CgCdr1, CgPdh1, and CgSnq2 are known to mediate azole resistance in the pathogenic fungus Candida glabrata. Activating mutations in CgPDR1, a zinc cluster transcription factor, result in constitutive up-regulation of these ABC-transporter genes but to varying degrees. We examined the genome-wide gene expression profiles of two matched azole-susceptible and –resistant C. glabrata clinical isolate pairs. Of all the genes identified in the gene expression profiles for these two matched pairs, there were 28 genes that were commonly up-regulated with CgCDR1 in both isolate sets including YOR1, LCB5, RTA1, POG1, HFD1, and several members of the FLO gene family of flocculation genes. We then sequenced CgPDR1 from each susceptible and resistant isolate and found two novel activating mutations that conferred increased resistance when expressed in a common background strain in which CgPDR1 had been disrupted. Microarray analysis comparing these re-engineered strains to their respective parent strains identified a set of commonly differentially-expressed genes, including CgCDR1, YOR1, and YIM1, as well as genes uniquely regulated by specific mutations. Our results demonstrate that while CgPdr1 activates a broad repertoire of genes, specific activating mutations result in the activation of discrete subsets of this repertoire. We examined the genome-wide gene expression profiles of two matched azole-susceptible and –resistant C. glabrata clinical isolate pairs to determine the core regulon of CgPDR1 as well as how different activating alleles of PDR1 can affect the differential expression of target genes. genotype: wildtype allele: SM1, 6856, SM1Dpdr1/PDR1-SM1, SM1Dpdr1/PDR1-6856 genotype: activating allele: SM3, 6955, SM1Dpdr1/PDR1-SM3, SM1Dpdr1/PDR1-6955

ORGANISM(S): [Candida] glabrata  

SUBMITTER: Kathy S Barker  Lijing Xu   Katherine S Barker   Ramin Homayouni   Kelly E Caudle   P D Rogers   Nathan P Wiederhold    

PROVIDER: E-GEOD-24168 | ArrayExpress | 2012-06-26

SECONDARY ACCESSION(S): GSE24168PRJNA130087

REPOSITORIES: GEO, ArrayExpress

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Publications

Genomewide expression profile analysis of the Candida glabrata Pdr1 regulon.

Caudle Kelly E KE   Barker Katherine S KS   Wiederhold Nathan P NP   Xu Lijing L   Homayouni Ramin R   Rogers P David PD  

Eukaryotic cell 20101230 3


The ABC transporters Candida glabrata Cdr1 (CgCdr1), CgPdh1, and CgSnq2 are known to mediate azole resistance in the pathogenic fungus C. glabrata. Activating mutations in CgPDR1, a zinc cluster transcription factor, result in constitutive upregulation of these ABC transporter genes but to various degrees. We examined the genomewide gene expression profiles of two matched azole-susceptible and -resistant C. glabrata clinical isolate pairs. Of the differentially expressed genes identified in the  ...[more]

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