Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Copper acts synergistically with fluconazole in Candida glabrata by compromising drug efflux, zinc homeostasis and sterol metabolism

ABSTRACT: In this study we used a transcriptomic approach to study the molecular determinants of the synergy between copper and fluconazole, in Candida glabrata, the second most frequent cause of invasive candidiasis. We demonstrate that copper acts together with fluconazole by downregulating three distinct pathways: azole efflux, ergosterol biosynthesis and zinc homeostasis. Coincidently, all these pathways are important for C. glabrata to cope with fluconazole stress. Therefore, when copper and fluconazole are combined cells fail to detoxify this drug and accumulate toxic methylated intermediates of sterol metabolism. This accumulation, possibly together with copper-induced lipid damages, should affect the activity of plasma membrane transporters, which impedes zinc uptake, leading to zinc depletion

ORGANISM(S): Nakaseomyces glabratus

PROVIDER: GSE162741 | GEO | 2022/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Copper acts synergistically with fluconazole in Candida glabrata by compromising drug efflux, zinc homeostasis and sterol metabolism

Project description:Copper acts synergistically with fluconazole in Candida glabrata by compromising drug efflux, zinc homeostasis and sterol metabolism

| PRJNA682828 | ENA

Transcriptional responses of Candida glabrata biofilm cells to fluconazole

Project description:In this study we performed a whole-transcriptome analysis of C. glabrata biofilm cells exposed to different environmental conditions and constraints in order to identify the molecular pathways involved in fluconazole resistance and understand how acidic pH niches, associated with the presence of acetic acid, are able to modulate these responses.

2019-01-01 | GSE121074 | GEO

Gene expression in response to fluconazole vs. the combination of fluconazole and osthole

Project description:Transcriptional profiling of Candida albicans comparing fluconazole treated cells with fluconazole and osthole treated cells

2017-04-24 | GSE84936 | GEO

RNA-sequencing analysis of fluconazole-treated wild-type and upc2A null cells [Fluconazole]

Project description:Purpose: Compare the fluconazole-induced transcriptome of isogenic wild-type and upc2A null cells. Methods: Prepare total RNA from wild-type and upc2A null cells grown under unstressed conditions or challenged with 50 microgram/ml fluconazole for 6 hours. Use standard RNA-seq to evaluate and compare the transcriptomic changes caused by fluconazole in the presence or absence of UPC2A. Results: These data established that over 100 genes were induced by fluconazole in a UPC2A-dependent manner. However, most fluconazole-induced genes (>500) did not require the presence of UPC2A. Fluconazole-induced genes included the expected genes involved in ergosterol biosynthesis but also large number of plasma membrane-localized transporters. Conclusions: These data suggest that Upc2A provided transcriptional co-regulation between membrane transporters and the lipid environment in which these proteins function. A significant portion of the fluconazole-induced transcriptome does not require the presence of Upc2A, suggesting the presence of other transcriptional circuits responsive to this pharmacologic block of ergosterol biosynthesis.

2021-09-23 | GSE182489 | GEO

Gene expression in response to fluconazole vs. the combination of fluconazole and berberine

Project description:Transcriptional profiling of Candida albicans comparing fluconazole treated cells with fluconazole- and berberine-treated cells, as well untreated cells with berberine treated cells

2013-11-14 | GSE43662 | GEO

Transcriptional responses of Candida glabrata biofilm cells to fluconazole

Project description:Transcriptional responses of Candida glabrata biofilm cells to fluconazole

| PRJNA495600 | ENA

Expression profilling of C. glabrata response to fluconazole and the role of the transcription factor Mar1 in such response

Project description:The goals of this study are to compare C. glabrata transcriptome profiling (RNA-seq) upon exposure to the antifungal fluconazole in order to assess antifungal response. The role of the transcription factor Mar1 is clarified through comparison of the transcrptome profiles of WT and Mar1 mutant cells. mRNA profiles of WT and ∆mar1 were generated by deep sequencing, in duplicate, using Illumina HiSeq. The sequence reads that passed quality filters were analyzed with TopHat followed by HTSeq.

2022-01-05 | GSE163158 | GEO

Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering (S. cerevisiae, C. glabrata, K. lactis)

Project description:Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.

2010-07-08 | GSE15710 | GEO

Loss-of-function ROX1 mutations suppress the fluconazole susceptibility of upc2A∆ mutation in Candida glabrata, implicating additional positive regulators of ergosterol biosynthesis

Project description:Two of the major classes of antifungal drugs in clinical use target ergosterol biosynthesis. Despite its importance, our understanding of the transcriptional regulation of ergosterol biosynthesis genes in pathogenic fungi is essentially limited to the role of hypoxia and sterol-stress induced transcription factors such as Upc2 and Upc2A as well as homologs of Sterol Response Element Binding (SREB) factors. To identify additional regulators of ergosterol biosynthesis in Candida glabrata, an important human fungal pathogen with reduced susceptibility to ergosterol biosynthesis inhibitors relative to other Candida spp., we used a serial passaging strategy to isolate suppressors of the fluconazole hypersusceptibility of a upc2A∆ deletion mutant. This led to the identification of loss of function mutants in two genes: ROX1, the homolog of a hypoxia gene transcriptional suppressor in Saccharomyces cerevisiae, and CST6, a transcription factor that is involved in the regulation of carbon dioxide response in C. glabrata. Here, we describe a detailed analysis of the genetic interaction of ROX1 and UPC2A. In the presence of fluconazole, loss of Rox1 function restores ERG11 expression to the upc2A∆ mutant and inhibits the expression of ERG3 and ERG6, leading to increased levels or ergosterol and decreased levels of the toxic sterol, 14α methyl-ergosta-8,24(28)-dien-3β, 6α-diol, relative to upc2A∆. Our observations establish that Rox1 is a negative regulator of ERG gene biosynthesis and indicate that a least one additional positive transcriptional regulator of ERG gene biosynthesis must be present in C. glabrata.

2021-12-20 | GSE191145 | GEO

Expression profilling of C. glabrata response to fluconazole in distinct growth conditions. Role of the Coregulator Pgd1 in such response.

Project description:The goal of this study is to compare the C. glabrata transcriptome profile (RNA-seq) upon exposure to the antifungal fluconazole in either liquid or solid medium and assess differential antifungal response. The role of the coregulator PGD1 is clarified through comparison of the transcriptome profiles of WT and PGD1 mutant cells. mRNA profiles of WT and ∆pgd1 were generated by deep sequencing, in triplicate, using Illumina NextSeq. The sequence reads that passed quality filters were analyzed with TopHat followed by HTSeq.

2022-03-31 | GSE174437 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data