Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CoCl2 Response in Cryptococcus neoformans

ABSTRACT: We investigated the effects of the hypoxia-mimetic CoCl2 on the gene expression of pathogenic fungus Cryptococcus neoformans. Keywords: compound treatment design Three biological repeats were performed using three independent RNA sets isolated from cells cultured on different days and the dye-reverse hybridizations were performed for all three sets. One set of RNA was also subjected to technical repeats.

ORGANISM(S): Filobasidiella neoformans

SUBMITTER: Yun Chang

PROVIDER: E-GEOD-11390 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans.

Lee Hyeseung H Bien Clara M CM Hughes Adam L AL Espenshade Peter J PJ Kwon-Chung Kyung J KJ Chang Yun C YC

Molecular microbiology 20070721 4

We investigated the effects of the hypoxia-mimetic CoCl2 in the pathogenic fungus Cryptococcus neoformans and demonstrated that CoCl2 leads to defects in several enzymatic steps in ergosterol biosynthesis. Sterol defects were amplified in cells lacking components of the Sre1p-mediated oxygen-sensing pathway. Consequently, Sre1p and its binding partner Scp1p were essential for growth in the presence of CoCl2. Interestingly, high copies of a single gene involved in ergosterol biosynthesis, ERG25, ...[more]

PMID: 17645443

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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. 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.

Dataset Information

CoCl2 Response in Cryptococcus neoformans

Publications

Cobalt chloride, a hypoxia-mimicking agent, targets sterol synthesis in the pathogenic fungus Cryptococcus neoformans.

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