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Series GSE21352 Query DataSets for GSE21352
Status Public on Jul 07, 2010
Title Azole Resistance Mechanism in Candida glabrata Oropharyngeal Isolates
Organism Nakaseomyces glabratus
Experiment type Expression profiling by array
Summary Microarray was used to analyze azole resistance of Candida glabrata oropharyngeal isolates from 7 hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis. Transcriptional profiling of the sequential-paired clinical isolates by microarray revealed 19 genes upregulated in the majority of resistant isolates compared to their paired-susceptible isolates. All seven resistant isolates had greater than two fold upregulation of CgPDR1, a master transcriptional regulator of PDR network, and all 7 resistant isolates showed upregulation of known CgPDR1-target genes. The altered transcriptome can be explained in part by the observation that all 7 resistant isolates had acquired a single nonsynonymous mutation in their CgPDR1 ORF. Four mutations occurred in the regulatory domain (L280P, L344S, G348A, S391L) and one in the activation domain (G943S) while two mutations (N764I, R772I) occurred in an undefined region. Association of azole resistance and the CgPDR1 mutations was investigated in the same genetic background by introducing the CgPDR1 sequences from one sensitive and five resistant isolates into a laboratory azole-sensitive strain (cgpdr1) via integrative transformation. The cgpdr1 strain was restored to wild-type fluconazole susceptibility when transformed with CgPDR1 from the susceptible isolate but became resistant when transformed with CgPDR1 from the resistant isolates. However, despite the identical genetic background, upregulation of CgPDR1 and CgPDR1-target genes varied between the 5 transformants, independent of the domain locations in which the mutations occurred. In sum, gain-of-function mutations in CgPDR1 not only contributed to the clinical azole resistance but different mutations had varying degrees of impact on the CgPDR1-target genes.
 
Overall design Seven pairs of oropharyngeal sequential isolates were chosen for study because each pair came from an individual hematopoietic stem cell transplant recipient receiving fluconazole. Seven groups consisted of 5 biological replicates in which a sensitive sample was paired with a resistant sample. Each group included 1 to 2 reciprocally labeled samples.
 
Citation(s) 20547810
Submission date Apr 15, 2010
Last update date Apr 30, 2013
Contact name Huei-Fung Tsai
E-mail(s) [email protected]
Phone 301-496-8993
Fax 301-480-0512
Organization name NIH/NIAID
Department LCID
Lab CMS
Street address 10 Center Dr. Bldg. 10 Rm. 11N228
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL8174 NIAID Cgaa -- Candida glabrata 6K
Samples (35)
GSM533563 14R/13S - repeat 1 - mAdbID:56799
GSM533564 14R/13S - repeat 2 - mAdbID:56828
GSM533565 14R/13S - repeat 3 - mAdbID:57026
Relations
BioProject PRJNA126107

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Supplementary file Size Download File type/resource
GSE21352_RAW.tar 20.6 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table
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