Transcriptional responses of Candida glabrata biofilm cells to fluconazole
Ontology highlight
ABSTRACT:
ORGANISM(S): Nakaseomyces glabratus
PROVIDER: GSE121074 | GEO | 2019/01/01
REPOSITORIES: GEO
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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:Transcriptional responses of Candida glabrata biofilm cells to fluconazole
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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: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: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:To examine the role of a glycosylphosphatidylinositol-linked aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata, transcriptional profiling analysis was carried out on wild-type and Cgyps1∆ cells grown in YNB medium (pH 5.5) and in YNB medium adjusted to pH 2.0. Genes involved in carbohydrate and amino acid metabolism, protein folding and stress response pathways were found to be differentially regulated in response to acidic environment in both the strains. To examine the role of a glycosylphosphatidylinositol-linked aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata, transcriptional profiling analysis was carried out on wild-type and Cgyps1∆ delta cells grown in YNB medium (pH 5.5) and in YNB medium adjusted to pH2.0. Genes involved in carbohydrate and amino acid metabolism, protein folding and stress response pathways were found to be differentially regulated in response to acidic environment in both the strains
2011-01-10 | GSE24267 | 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:Candida glabrata is a clinically relevant human pathogen with ability to form high recalcitrant biofilms that contribute to the establishment and persistence of infection. A defining trait of biofilms is the auto-produced matrix, which is suggested to have structural, virulent and protective roles. Thus, elucidation of matrix components, their function and modulation by host environment is crucial to disclose their role in C. glabrata pathogenesis. As a major step toward this end, this study aimed to reveal, for the first time, the matrix proteome of C. glabrata biofilms, to characterize it with bioinformatic tools and to study its modulation by the environmental pH (acidic and neutral). The results showed the presence of several pH-specific matrix proteins (51 acidic- and 206 neutral-specific) and also proteins commonly found at both pH conditions (236). Of note, several proteins related to β-glucan metabolism, which have a potential role in the delivery/organization of matrix glucans, were found in both conditions but in much higher quantity under the neutral environment. Additionally, proteins with roles in adhesion, including epithelial adhesins, and virulence-related, including yapsins, were found among pH-specific and non-specific matrix proteins. Importantly, several proteins seem to have a non-canonical secretion pathway and Pdr1 was found to be a potential regulator of matrix proteome. Overall, this study indicates a relevant impact of environmental cues in the matrix proteome and provides a unique resource for further functional investigation of matrix proteins, contributing to the identification of potential targets for the development of new therapies against C. glabrata biofilms.
2024-02-22 | PXD022597 | Pride
Project description:The vaginal acidic environment potentiates the formation of Candida glabrata biofilms, leading to complicated and recurrent infections. Importantly, the regulation of biofilm matrix is known to contribute to the recalcitrant features of Candida biofilms. In this study we reveal a new matrix regulator of C. glabrata acidic biofilms, Zap1, and analyzed its modulation of the transcriptome (by microarrays) and matrix proteome (by LC-MS/MS). For that, the deletion mutant zap1Δ and its complemented strain zap1Δ::ZAP1 were constructed and their biofilms were developed at pH 4 (adjusted with lactic acid). The results revealed that Zap1 is a negative regulator of the total amount of protein and carbohydrate in the biofilm matrix. Accordingly, various genes and matrix proteins with predicted functions in the regulation of carbohydrate metabolism, sugar binding, sugar transport and adhesion (including Epa family) were found to be repressed by Zap1. Nevertheless, the results also suggested that Zap1 is essential to the delivery and organization of some matrix components. Indeed, Zap1 was required to the secretion of 122 proteins to the matrix and induced the expression of 557 genes, including various targets involved in glucan-metabolism. Additionally, Zap1 induced targets with roles in virulence, resistance to antifungals and host immunity evasion, including yapsins, ERG family and moonlighting proteins. Zap1 was also required to the secretion of acidic-specific matrix proteins, indicating a contribution to the response to the acidic environment. Overall, this study demonstrates that Zap1 is a relevant regulator of biofilm matrix, contributing to a better understanding of C. glabrata acidic biofilms.
2024-10-28 | PXD044153 | Pride
Project description:Transcriptomics analysis of the evolution of a C. glabrata clinical isolate (044) from azole susceptibility to posaconazole resistance (21st day), clotrimazole resistance (31st day) and fluconazole and voriconazole resistance (45th day), induced by longstanding incubation with fluconazole (16mg/mL).
2018-11-16 | E-MTAB-6787 | biostudies-arrayexpress