Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata (part 2)
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida glabrata
SUBMITTER: Dominique Sanglard
PROVIDER: E-GEOD-23828 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:In this study, we aimed to determine genome-wide changes in gene expression driven by seven individual CgPDR1 hyperactive alleles as compared to wild-type allele to identify i) the CgPdr1p target genes differentially expressed in presence of CgPDR1 hyperactive alleles and ii) potential virulence factor(s) regulated by CgPDR1 hyperactive alleles. Microarray experiments revealed a high number of genes (ranging from 80 to 400 genes) differentially regulated by individual CgPDR1 hyperactive alleles. Gene expression was measured in 7 C. glabrata laboratory strains (SFY101, SFY103, SFY105, SFY109, SFY111, SFY115, SFY116) expressing different CgPDR1 hyperactive alleles, in 1 strain (SFY114) expressing a wild-type CgPDR1 allele and in one strain deleted for CgPDR1. The one-color system was used. 3 independent experiments were performed using 3 biological replicates for each strain.
2010-12-31 | E-GEOD-23827 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE23827: Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata (part 1) GSE23828: Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata (part 2) Refer to individual Series
2010-12-31 | E-GEOD-23829 | biostudies-arrayexpress
Project description:In this study, we aimed to determine genome-wide changes in gene expression driven by seven individual CgPDR1 hyperactive alleles as compared to wild-type allele to identify i) the CgPdr1p target genes differentially expressed in presence of CgPDR1 hyperactive alleles and ii) potential virulence factor(s) regulated by CgPDR1 hyperactive alleles. Microarray experiments revealed a high number of genes (ranging from 80 to 400 genes) differentially regulated by individual CgPDR1 hyperactive alleles.
2010-12-31 | GSE23828 | GEO
Project description:In this study, we aimed to determine genome-wide changes in gene expression driven by seven individual CgPDR1 hyperactive alleles as compared to wild-type allele to identify i) the CgPdr1p target genes differentially expressed in presence of CgPDR1 hyperactive alleles and ii) potential virulence factor(s) regulated by CgPDR1 hyperactive alleles. Microarray experiments revealed a high number of genes (ranging from 80 to 400 genes) differentially regulated by individual CgPDR1 hyperactive alleles.
2010-12-31 | GSE23827 | GEO
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.
2010-07-07 | E-GEOD-21355 | biostudies-arrayexpress
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.
2010-07-07 | GSE21355 | GEO
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.
2010-07-07 | GSE21352 | GEO
Project description:The pathogenic yeast species Candida glabrata has an intrinsically high resilience to azoles and a rapid capability of acquiring resistance. Azole-resistant clinical strains derive mostly from them encoding hyperactive mutants of the CgPdr1 regulator, however, strains encoding wild-type CgPdr1 variants were identified suggesting a role for CgPdr1-independent mechanisms in acquisition of resistance in vivo. Seven azole-resistant C. glabrata isolates were found to encode CgPdr1 gain-of-function variants, two, I392M and I803T, being herein described for the first time. OMICS profile of the sole azole-resistant strain encoding a wild-type CgPDR1 allele revealed that these cells over-express several genes described for providing protection against azoles, while down-regulating genes described to increase sensitivity to these drugs. Over-expression of genes required for metabolism and transport of sterols to compensate the azole-induced inhibition of Erg11 and a more active calcineurin pathway are other mechanisms suggested to underlie azole resistance in ISTB218.
2022-05-16 | GSE166841 | GEO
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.
2010-07-07 | E-GEOD-21352 | biostudies-arrayexpress
Project description:Two C. glabrata related isolates recovered from the same patient undergoing azole therapy were characterized. The first isolate, BPY40, is azole-susceptibleand the second, BPY41, is azole-resistant. To determine whether the petite mutation conferred a selective advantage during host infection, the virulence of BPY40 and BPY41 was assessed in mice. Surprisingly, the petite mutant, even if showing in vitro growth deficiency as compared to BPY40, was more virulent than BPY40 both in intravenous and vaginal murine infection models. The increased virulence of the petite mutant correlated with a drastic gain of fitness in mice as compared to its parental isolate. Genome-wide changes in gene expression driven by the petite mutation were analyzed by microarrays. Enrichment of specific biological processes (oxido-reductive metabolism, stress response) was observed in BPY41, all consistent with mitochondrial dysfunction. Finally, some genes involved in cell wall genome-wide changes in gene expression driven by the petite mutation were analyzed by microarrays. Enrichment of specific biological processes (oxido-reductive metabolism, stress response) was observed in BPY41, all consistent with mitochondrial dysfunction. Gene expression was measured in 2 related C. glabrata clinical isolates (BPY40 and BPY41). The one-color system was used . 3 independent experiments were performed using 3 biological replicate for each strain.
2010-12-31 | E-GEOD-23826 | biostudies-arrayexpress