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

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

PROVIDER: PRJNA729966 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14536300_1.fastq.gz	Fastqsanger.gz
	SRR14536300_2.fastq.gz	Fastqsanger.gz
	SRR14536301_1.fastq.gz	Fastqsanger.gz
	SRR14536301_2.fastq.gz	Fastqsanger.gz
	SRR14536302_1.fastq.gz	Fastqsanger.gz

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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

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

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Expression profilling of C. glabrata response to fluconazole and the role of the transcription factor Rpn4 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 Rpn4 is clarified through comparison of the transcrptome profiles of WT and Rpn4 mutant cells. mRNA profiles of WT and ∆rpn4 were generated by deep sequencing, in duplicate, using Illumina HiSeq. The sequence reads that passed quality filters were analyzed with TopHat followed by HTSeq. RNA-seq data allowed to identify genes whose expression is regulated by the Rpn4 transcription factor (80 positively regulated and 212 negatively regulated) with a log2fold change ≥0.5 and p value <0.05. The transcriptomics data was then used to guide further work to detail the function of Rpn4.

2019-09-27 | GSE129349 | GEO

Expression profilling of C. glabrata response to fluconazole and the role of the transcription factor Rpn4 in such response

Project description:Expression profilling of C. glabrata response to fluconazole and the role of the transcription factor Rpn4 in such response

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

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

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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.

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

Project description: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

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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.

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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.

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

2010-07-08 | E-GEOD-15710 | biostudies-arrayexpress