Dataset Information

Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant recipient.

ABSTRACT: We describe the acquisition of flucytosine, azole, and caspofungin resistance in sequential Candida glabrata bloodstream isolates collected from a bone marrow transplant patient with clinical failure. Point mutations in C. glabrata FUR1 (CgFUR1) and CgFKS2 and overexpression of CgCDR1 and CgCDR2 were observed in resistant isolates.

SUBMITTER: Chapeland-Leclerc F

PROVIDER: S-EPMC2826023 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant recipient.

Chapeland-Leclerc Florence F Hennequin Christophe C Papon Nicolas N Noël Thierry T Girard Aurélie A Socié Gérard G Ribaud Patricia P Lacroix Claire C

Antimicrobial agents and chemotherapy 20091228 3

We describe the acquisition of flucytosine, azole, and caspofungin resistance in sequential Candida glabrata bloodstream isolates collected from a bone marrow transplant patient with clinical failure. Point mutations in C. glabrata FUR1 (CgFUR1) and CgFKS2 and overexpression of CgCDR1 and CgCDR2 were observed in resistant isolates. ...[more]

PMID: 20038613

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Project description: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. Two groups (C1S/84 and C16R/84) consisted of 4 biological replicates in which a complemented strain sample was paired with the laboratory wild type strain 84 sample. Each group included 1 reciprocally labeled sample.

Dataset Information

Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant recipient.

Publications

Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant recipient.

Similar Datasets

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