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ABSTRACT:
PROVIDER: PRJNA745548 | ENA |
REPOSITORIES: ENA
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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:Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. We previously identified an activator-targeted ~85 amino acid three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11 Mediator subunits in fungi. The Gal11 KIX domain is engaged by pleiotropic drug resistance transcription factor (Pdr1) orthologues, key regulators of the multidrug resistance (MDR) pathway in S. cerevisiae and in the clinically important human pathogen Candida glabrata. Drug-resistant clinical isolates of C. glabrata most commonly harbour point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional activation pathway may represent a lynchpin in C. glabrata MDR. We have now carried out sequential biochemical and in vivo high-throughput screens to identify small molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation in both S. cerevisiae and C. glabrata and re-sensitizes drug-resistant C. glabrata to effective azole antifungal concentrations in vitro and in animal models for disseminated and urinary tract C. glabrata infection.
2015-12-15 | GSE74361 | GEO
Project description:Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. We previously identified an activator-targeted ~85 amino acid three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11 Mediator subunits in fungi. The Gal11 KIX domain is engaged by pleiotropic drug resistance transcription factor (Pdr1) orthologues, key regulators of the multidrug resistance (MDR) pathway in S. cerevisiae and in the clinically important human pathogen Candida glabrata. Drug-resistant clinical isolates of C. glabrata most commonly harbour point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional activation pathway may represent a lynchpin in C. glabrata MDR. We have now carried out sequential biochemical and in vivo high-throughput screens to identify small molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation in both S. cerevisiae and C. glabrata and re-sensitizes drug-resistant C. glabrata to effective azole antifungal concentrations in vitro and in animal models for disseminated and urinary tract C. glabrata infection. Samples are generated in triplicate for four conditions (DMSO/vehicle-treated, iKIX1-treated, DMSO/vehicle and ketoconazole-treated. and iKIX1-ketoconazole treated) in both Saccharomyces cerevisiae and Candida glabrata
2015-12-15 | E-GEOD-74361 | biostudies-arrayexpress
Project description:The transcription profile of Candida glabrata grown under two different Niacin limitation conditions were determined. Condition 1 is comparing log phase C. glabrata cells (O.D. 0.5-0.6) grown in synthetic medium containing 0.016 uM versus 3.25 uM nicotinic acid (NA), a common form of Niacin. The NA concentration of 3.25 uM is the standard concentration in synthetic complete (SC) medium. Condition 2 is comparing log phase C. glabrata cells (O.D. 0.4-0.6) grown in 3 individual human urine samples (supplemented with 2% glucose) versus in SC medium. Keywords: transcriptional profiling by microarray
2006-12-22 | GSE6582 | GEO
Project description:During sexual transmission of HIV-1 from male to female partners, the vagina is the initial site of contact with HIV infected semen. The mechanism of HIV traversing the CD4 negative multi-layered stratified squamous epithelial barrier of the vagina to infect sub-epithelial susceptible immune cells, is hitherto unknown. HIV gp120 binds to several host proteins on vaginal epithelial cells. To gain an insight into the physiologic changes that may occur in vaginal epithelial cells in response to interactions with HIV gp120, and obtain an understanding of the molecular mechanisms by which HIV breaches the vaginal epithelium, a global snap shot of gene expression profiles in the vaginal epithelial cell line Vk2/E6E7, treated with HIV gp120 was determined. The vaginal epithelial cell line Vk2/E6E7 was treated with HIV gp120 (83nM) for 24 hr, and Agilent one colour, microarrays were performed. Agilent one-color experiment,Organism: Human ,Agilent-Custom Whole Genome Human 8x60k designed by Genotypic Technology Pvt. Ltd. (AMADID: 027114), Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)
2014-03-01 | E-GEOD-44914 | biostudies-arrayexpress
Project description:To delineate the interaction of Candida glabrata with host immune cells, we performed genome-wide transcriptional profiling analysis on THP-1 macrophage-internalized wild-type and chromatin remodeling defective mutant (Cgrsc3-a∆ and Cgrtt109∆) yeasts. Genes implicated in ergosterol biosynthesis, and high-affinity iron uptake and homeostasis were found to be down-regulated in C. glabrata wild-type and mutant cells upon macrophage internalization. Additionally, global gene expression profiles of RPMI-grown and macrophage-ingested Cgrsc3-a∆ and Cgrtt109∆ cells revealed down-regulation of genes involved in mitochondrial respiration under normal growth conditions and induction of genes required for generation of precursors of metabolites and energy upon macrophage internalization. To examine the behavior of Candida glabrata wild-type and chromatin remodeling defective mutants upon internalization by differentiated human monocytic THP-1 cells, we compared the transcript profiles of 10 hour RPMI-grown with those of 10 hour THP-1 macrophage internalized C. glabrata cells. Additionally, early transcriptional response of C. glabrata wild-type cells to macrophage internal milieu was examined post 2 hour THP-1 macrophage infection.
2012-08-18 | GSE38953 | GEO
Project description:To delineate the interaction of Candida glabrata with host immune cells, we performed genome-wide transcriptional profiling analysis on THP-1 macrophage-internalized wild-type and chromatin remodeling defective mutant (Cgrsc3-aM-bM-^HM-^F and Cgrtt109M-bM-^HM-^F) yeasts. Genes implicated in ergosterol biosynthesis, and high-affinity iron uptake and homeostasis were found to be down-regulated in C. glabrata wild-type and mutant cells upon macrophage internalization. Additionally, global gene expression profiles of RPMI-grown and macrophage-ingested Cgrsc3-aM-bM-^HM-^F and Cgrtt109M-bM-^HM-^F cells revealed down-regulation of genes involved in mitochondrial respiration under normal growth conditions and induction of genes required for generation of precursors of metabolites and energy upon macrophage internalization. To examine the behavior of Candida glabrata wild-type and chromatin remodeling defective mutants upon internalization by differentiated human monocytic THP-1 cells, we compared the transcript profiles of 10 hour RPMI-grown with those of 10 hour THP-1 macrophage internalized C. glabrata cells. Additionally, early transcriptional response of C. glabrata wild-type cells to macrophage internal milieu was examined post 2 hour THP-1 macrophage infection. Agilent one-color experiment, Organism: Yeast (Candida glabrata)
2012-08-18 | E-GEOD-38953 | biostudies-arrayexpress
Project description:In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are jointly required for induction of phosphate response genes and survival in phosphate starvation conditions. In the related human commensal and pathogen C. glabrata, Pho4 is required but Pho2 is dispensable for survival in phosphate-limited conditions and is only partially required for inducing the phosphate response genes. This reduced dependence on Pho2 evolved in C. glabrata and closely related species. Pho4 orthologs that are less dependent on Pho2 induce more genes when introduced into the S. cerevisiae background, and Pho4 in C. glabrata both binds to more sites and induces more genes with expanded functional roles compared to Pho4 in S. cerevisiae. We used Biotin-assisted Chromatin-ImmunoPrecipitation followed by high-throughput sequencing (BioChIP-seq) to identify the binding locations of Pho4 from both S. cerevisiae and C. glabrata in the S. cerevisiae background lacking the negative regulator Pho80, and either with or without Pho2.
2017-04-15 | GSE97797 | GEO
Project description:In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are jointly required for induction of phosphate response genes and survival in phosphate starvation conditions. In the related human commensal and pathogen C. glabrata, Pho4 is required but Pho2 is dispensable for survival in phosphate-limited conditions and is only partially required for inducing the phosphate response genes. This reduced dependence on Pho2 evolved in C. glabrata and closely related species. Pho4 orthologs that are less dependent on Pho2 induce more genes when introduced into the S. cerevisiae background, and Pho4 in C. glabrata both binds to more sites and induces more genes with expanded functional roles compared to Pho4 in S. cerevisiae. We used Chromatin-ImmunoPrecipitation with exonucleas followed by high-throughput sequencing (BioChIP-seq) to identify the binding locations of Pho4 from both S. cerevisiae and C. glabrata in the S. cerevisiae background lacking the negative regulator Pho80, and either with or without Pho2.
2017-04-15 | GSE97798 | GEO