Transcriptional responses of Candida glabrata biofilm cells to fluconazole
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ABSTRACT:
PROVIDER: PRJNA495600 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7993590.fastq.gz | Fastqsanger.gz | |||
| SRR7993600.fastq.gz | Fastqsanger.gz | |||
| SRR7993591.fastq.gz | Fastqsanger.gz | |||
| SRR7993601.fastq.gz | Fastqsanger.gz | |||
| SRR7993582.fastq.gz | Fastqsanger.gz |
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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
Project description:Transcriptional profiling of Candida glabrata zap1Δ and zap1Δ::ZAP1 strains, comparing cells grown under planktonic and biofilm-inducing conditions. Goal was to analyse the effect of ZAP1 deletion in the transcriptomic profile of C. glabrata biofilm cells (in comparision to planktonic cells), under acidic conditions, in order to study the function of the Zap1 transcription factor in C. glabrata biofilm matrix production.
2024-08-08 | GSE226915 | GEO
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
2022-06-01 | GSE162741 | GEO
Project description:This study explored the transcriptional change of Candida glabrata cells due to GCN5 deletion. We also compared the transcriptional responses to fluconazole and micafungin in WT and gcndelta cells relative to respective no drug controls.
2022-01-28 | GSE194310 | GEO
Project description:Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Derg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum.
2023-02-08 | GSE202656 | GEO
Project description:Aim: of the study was to compare the transcriptomic profiling of planktonic and biofilm growth phase of clinical isolate of Candida glabrata Methodology: RNA was extracted using Hi-PurA yeast RNA purification kit from biofilm and planktonic growth phase and sequenced by Illumina Hi-Seq 2500 platform with 250bp paired chemistry Results: we got 959 significantly Differential Expressed Genes DEGs (logFC => 1.5) acconts for 18.11 % in which 596 (11.26 %) are getting downregulated and 363 (6.85%) upregulated in the biofilm growth mode. We validated 8 genes by qPCR Conclusion: Comprehensive analysis of the large expression gene sets generated from experimental conditions (Planktonic vs Biofilm) by RNA Seq revealed the unique network of genes associated with this intricate and complex process. We observed that Differentially Expressed Genes (DEGs) associated with Glyoxylate and Dicarboxylate metabolism, Carbon-Carbon lyase activity
2021-06-09 | GSE152789 | GEO
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
Project description:Candida spp. are commensal opportunistic fungal pathogens that often colonize and infect mucosal surfaces of the human body. Candida, along with other microbes in the microbiota, generally grow as biofilms in a polymicrobial environment. Due to the nature of cellular growth in a biofilm (such as production of a protective extracellular matrix) and the recalcitrance of biofilms, infections involving biofilms are very difficult to treat with antibiotics and perpetuate the cycle of infection. The two most commonly isolated Candida spp. from Candida infections are Candida albicans and Candida glabrata, and the presence of both of these species results in increased patient inflammation and overall biofilm formation. This work aims to investigate the interspecies interactions between C. albicans (Ca) and C. glabrata (Cg) in co-culture through transcriptome analysis over the course of biofilm growth. We report that during co-culture, lipid biosynthesis and transporter genes were significantly modulated in both Ca and Cg. Differentially expressed genes in Ca during co-culture growth included putative transporter genes (C2_02180W_A and C1_09210C_B; up-regulated), amino acid biosynthesis (ARO7; up-regulated most in Ca:Cg 1:3), and lipid-related genes (LIP3 and IPT1; down-regulated). Differentially expressed genes in Cg in co-culture included putative transmembrane transporters (CAGL0H03399g and CAGL0K04609g; up-regulated), an oxidative stress response gene (CAGL0E04114g; down-regulated most in Ca:Cg 1:3), genes involved in the TCA cycle (LYS12 and CAGL0J06402g; down-regulated), and several genes involved in cell wall/membrane biosynthesis (SEC53, GAS2, VIG9; down-regulated). Additionally, confocal microscopy was utilized for membrane lipid analysis between monoculture and co-culture biofilms. Through filipin-stained lipid analysis, we found that there was a significant increase in cell membrane lipid content in Ca:Cg 1:3 biofilms compared to Ca and Ca:Cg 3:1 biofilms. These results suggest substantial modifications of both cell wall, cell membrane, and transporters in both Ca and Cg during the time course of co-culture growth, which allows for increased biofilm formation and virulence in Candida co-culture biofilms.
2019-05-31 | GSE119059 | GEO
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
Project description:The different expression of Candida glabrata haploid and diploid.
2021-04-30 | GSE173617 | GEO