ITRAQ results of Candida albicans treated with FLC and BE
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida Albicans
SUBMITTER: 
Yuanying Jiang
PROVIDER: PXD028207 | iProX | Fri Sep 03 00:00:00 BST 2021
REPOSITORIES: iProX
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Project description:Transcriptional profiling of Candida albicans cells comparing control untreated C. albicans cells with sulfite-treated C. albicans cells. Sulfite is a toxic molecule that C. albicans encounters in its human host. Both wild type and ∆zcf2 mutant cells were used. The goal was to determine the effects of sulfite on C. albicans gene expression, and to determine which of the genes areZcf2-depedent.
2016-12-03 | GSE90819 | GEO
Project description:Azole antifungal agents such as fluconazole exhibit fungistatic activity against Candida albicans. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence fluconazole susceptibility, we sought to identify transcription factors (TFs) involved in this process. From a collection of C. albicans strains disrupted for genes encoding TFs (Homann et al., PLoS Genet. 2009;5:e1000783), four exhibited a marked reduction in minimum fungicidal concentration (MFC) in both RPMI and YPD media. One of these, UPC2, has been previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (CAS5) was unable to recover from fluconazole exposure at concentrations as low as 2 µg/mL after 72 hours in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid media containing 10 µg/mL fluconazole, and exhibited increased susceptibility by time-kill analysis. CAS5 disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However, CAS5 disruption in strains with specific resistance mutations in ergosterol biosynthesis or efflux pumps resulted in a moderate reduction in MIC and MFC. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of CAS5 in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences susceptibility of C. albicans to fluconazole. Further delineation of this transcriptional network may identify targets for potential co-therapeutic strategies to enhance the activity to the azole class of antifungals.
2014-05-24 | GSE57930 | GEO
Project description:Given the risk of Candida albicans overgrowth in the gut, novel complementary therapies should be developed to reduce fungal dominancy. This study highlights the antifungal characteristics of a Bacillus subtilis-derived secondary metabolite, surfactin with high potential against C. albicans. Surfactin inhibited the growth of C. albicans following a 1-hour exposure, in addition to reduced adhesion and morphogenesis. Specifically, surfactin did not affect the level of reactive oxygen species but increased the level of reduced glutathione. Surprisingly, ethanol production was increased following 2 hours of surfactin exposure. Surfactin treatment caused a significant reduction in intracellular iron, manganese and zinc content compared to control cells, whereas the level of copper was not affected. Alongside these physiological properties, surfactin also enhanced fluconazole efficacy. To gain detailed insights into the surfactin-related effects on C. albicans, genome-wide gene transcription analysis was performed. Surfactin treatment resulted in 1390 differentially expressed genes according to total transcriptome sequencing (RNA-Seq). Of these, 773 and 617 genes with at least a 1.5-fold increase or decrease in transcription, respectively, were selected for detailed investigation. Several genes involved in morphogenesis or related to metabolism (e.g., glycolysis, ethanol and fatty acid biosynthesis) were down-regulated. Moreover, surfactin decreased the expression of ERG1, ERG3, ERG9, ERG10 and ERG11 involved in ergosterol synthesis, whereas genes associated with ribosome biogenesis and iron metabolism and drug transport-related genes were up-regulated. Our data demonstrate that surfactin significantly influences the physiology and gene transcription of C. albicans, and could contribute to the development of a novel innovative complementary therapy.
2022-06-02 | GSE199383 | GEO
Project description:Candida albicans is associated with humans as both a harmless commensal organism and a pathogen. Cph2 is a transcription factor whose DNA binding domain is similar to mammalian sterol response element binding proteins (SREBPs). SREBPs are master regulators of cellular cholesterol levels, and are highly conserved from fungi to mammals. However, ergosterol biosynthesis is regulated by the zinc finger transcription factor Upc2 in C. albicans and several other yeasts. Cph2 is not necessary for ergosterol biosynthesis, but important for colonization in the murine gastrointestinal tract. Here we demonstrate that Cph2 is a membrane-associated transcription factor that is processed to release the N-terminal DNA binding domain like SREBPs; but its cleavage is not regulated by cellular levels of ergosterol or oxygen. ChIP-Seq shows that Cph2 binds to the promoters of HMS1 and other components of the regulatory circuit for GI tract colonization. In addition, 50% of Cph2 targets are also bound by Hms1 and other factors of the regulatory circuit. Several common targets function at the head of the glycolysis pathway. Thus, Cph2 is an integral part of the regulatory circuit for GI colonization that regulates glycolytic flux. RNA-seq shows a significant overlap in genes differentially regulated by Cph2 and hypoxia, and Cph2 is important for optimal expression of some hypoxia-responsive genes in glycolysis and the citric acid cycle. We suggest that Cph2 and Upc2 regulate hypoxia-responsive expression in different pathways, consistent with a synthetic lethal defect of the cph2 upc2 double mutant in hypoxia.
2015-08-05 | GSE71728 | GEO
Project description:Candida albicans is associated with humans as both a harmless commensal organism and a pathogen. Cph2 is a transcription factor whose DNA binding domain is similar to mammalian sterol response element binding proteins (SREBPs). SREBPs are master regulators of cellular cholesterol levels, and are highly conserved from fungi to mammals. However, ergosterol biosynthesis is regulated by the zinc finger transcription factor Upc2 in C. albicans and several other yeasts. Cph2 is not necessary for ergosterol biosynthesis, but important for colonization in the murine gastrointestinal tract. Here we demonstrate that Cph2 is a membrane-associated transcription factor that is processed to release the N-terminal DNA binding domain like SREBPs; but its cleavage is not regulated by cellular levels of ergosterol or oxygen. ChIP-Seq shows that Cph2 binds to the promoters of HMS1 and other components of the regulatory circuit for GI tract colonization. In addition, 50% of Cph2 targets are also bound by Hms1 and other factors of the regulatory circuit. Several common targets function at the head of the glycolysis pathway. Thus, Cph2 is an integral part of the regulatory circuit for GI colonization that regulates glycolytic flux. RNA-seq shows a significant overlap in genes differentially regulated by Cph2 and hypoxia, and Cph2 is important for optimal expression of some hypoxia-responsive genes in glycolysis and the citric acid cycle. We suggest that Cph2 and Upc2 regulate hypoxia-responsive expression in different pathways, consistent with a synthetic lethal defect of the cph2 upc2 double mutant in hypoxia.
2015-08-10 | GSE71902 | 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:This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 454 genes compared to synchronous ground controls, which represented 8.4% of the analyzed ORFs. Spaceflight-cultured C. albicans induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to more normal bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in the actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, actin cytoskeleton, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed. This study represents an important basis for the assessment of the risk that commensal flora could play during spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.
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Project description:Candida albicans is associated with humans as both a harmless commensal organism and a pathogen. Cph2 is a transcription factor whose DNA binding domain is similar to mammalian sterol response element binding proteins (SREBPs). SREBPs are master regulators of cellular cholesterol levels, and are highly conserved from fungi to mammals. However, ergosterol biosynthesis is regulated by the zinc finger transcription factor Upc2 in C. albicans and several other yeasts. Cph2 is not necessary for ergosterol biosynthesis, but important for colonization in the murine gastrointestinal tract. Here we demonstrate that Cph2 is a membrane-associated transcription factor that is processed to release the N-terminal DNA binding domain like SREBPs; but its cleavage is not regulated by cellular levels of ergosterol or oxygen. ChIP-Seq shows that Cph2 binds to the promoters of HMS1 and other components of the regulatory circuit for GI tract colonization. In addition, 50% of Cph2 targets are also bound by Hms1 and other factors of the regulatory circuit. Several common targets function at the head of the glycolysis pathway. Thus, Cph2 is an integral part of the regulatory circuit for GI colonization that regulates glycolytic flux. RNA-seq shows a significant overlap in genes differentially regulated by Cph2 and hypoxia, and Cph2 is important for optimal expression of some hypoxia-responsive genes in glycolysis and the citric acid cycle. We suggest that Cph2 and Upc2 regulate hypoxia-responsive expression in different pathways, consistent with a synthetic lethal defect of the cph2 upc2 double mutant in hypoxia. Genome binding/occupancy profiling by high throughput sequencing. ChIP-seq of Cph2 was carried out in a wild-type strain carrying N-terminal myc-tagged Cph2 under the MAL2 promoter (MAL2-myc-Cph2N). IP and INPUT samples from 2 independent experiments, as well as a sample of untagged wild-type control, were sequenced.
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Project description:Candida albicans is the most common human fungal pathogen in immunocompromised individuals. With the emergence of clinical fungal resistance, there is an urgent demand to develop novel antifungal agents. The antibacterial peptide (AMP) is an important component in the innate immune system and has a good therapeutic effect on patients infected with microorganisms. AMP-17, a novel AMP from Musca domestica, has an antifungal effect against C. albicans, but the mechanism of antifungal action remains unclear. In this study, we performed proteomic analysis of C. albicans treated AMP-17 and No drug using a combination of a series of cutting-edge technologies, including TMT labeling, HPLC classification and quantitative proteomics based on mass spectrometry. A total of 3,931 proteins were identified, of which 3,600 contained quantitative information. With a 1.5-fold change threshold and a t-test p-value <0.05 as a standard, 423 differentially expressed proteins (DEPs) were up-regulated and 180 differentially expressed proteins (DEPs) were down-regulated in the quantitative AMP_17/con comparison group. In these DEPs, proteins associated with ergosterol biosynthesis, oxidative stress and cell wall were identified as significantly up-regulated, while proteins involved in fatty acid biosynthesis were identified as significantly down-regulated. In addition, using the KEGG enrichment assay, seven significant KEGG pathways were identified, primarily involved in oxidative phosphorylation, propionic acid metabolism, and fatty acid metabolism. These results showed that AMP-17 induces a complex organism response to C. albicans, indicating that AMP-17 can inhibit growth by affecting multiple targets in C. albicans cells.
2019-10-23 | PXD015469 | Pride
Project description:Purpose: To explore the influence of Candida albicans treatment in mice intestinal epithelia. Method: 108 CFU C. albicans or PBS was gavaged to Apoe-/- mice every 3 days for 2 weeks. mRNA profiles were generated by deep sequencing.Results: Several signaling pathways were changed after C. albicans treatment, including response to hypoxia pathway.
2024-04-09 | GSE263509 | GEO