Candida albicans
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PROVIDER: PRJNA389570 | ENA |
REPOSITORIES: ENA
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Project description:The Transcriptional Stress Response of Candida albicans to Weak Organic Acids
| PRJNA213618 | ENA
Project description:Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal microbiota were shown to keep C. albicans colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displayed a synergistic effect in vitro with the absence of glucose in medium of culture, which underline the complex interaction that C. albicans faces in its natural environment. Inactivation of the transcriptional regulator MIG1 in C. albicans results in a lack of sensitivity to this synergistic outcome. To decipher C. albicans transcriptional responses to glucose, WOAs and the role of MIG1, we performed RNA sequencing on four biological replicates exposed to combinations of these 3 parameters. We were able to characterise the i) glucose response, ii) response to acetic and butyric acid, iii) MIG1 regulation of C. albicans and iv) genes responsible for WOAs resistance. We identified a group of 6 genes linked to WOAs sensitivity in a glucose-MIG1-dependent manner and inactivated one of these genes, the putative glucose transporter HGT16, in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOAs resistance in absence of glucose. This result points towards a mechanism of WOAs sensitivity in C. albicans involving membrane transporters which could be exploited to control yeast colonisation in human body niches.
2017-10-03 | GSE99767 | GEO
Project description:The highly conserved heterotrimeric protein kinase SNF1 is important for metabolic adaptations in the pathogenic yeast Candida albicans. A key function of SNF1 is to inactivate the repressor protein Mig1 and thereby allow the expression of genes that are required for the the utilization of alternative carbon sources when the preferred carbon source glucose is absent or becomes limiting. However, how SNF1 controls Mig1 activity in C. albicans has remained elusive. Using a phosphoproteomic approach, we found that Mig1 is phosphorylated at multiple serine residues. Replacement of these serine residues by nonphosphorylatable alanine residues strongly increased the repressor activity of Mig1 in cells lacking a functional SNF1 complex, indicating that additional protein kinases are involved in the regulation of Mig1. Unlike wild-type Mig1, whose levels strongly decreased when the cells were grown on sucrose or glycerol instead of glucose, the levels of a mutant Mig1 protein lacking nine phosphorylation sites remained high under these conditions. Despite the increased protein levels and the absence of multiple phosphorylation sites, cells with a functional SNF1 complex could still sufficiently inhibit the hyperactive Mig1 to enable wild-type growth on alternative carbon sources. In line with this, phosphorylated forms of the mutant Mig1 were still detected in the presence and absence of a functional SNF1, demonstrating that Mig1 contains additional, unidentified phosphorylation sites and that downstream protein kinases are involved in the control of Mig1 activity by SNF1.
2023-10-27 | PXD045393 | Pride
Project description:Purpose: Candida albicans avidly uses multiple carbon sources that are less preferred by related species. This project compared transcriptional profiles of cells growing in media containing these nutrients relative to glucose Methods: C. albicans strain SC5314 was incubated in minimal YNB media containing 2% glucose, casamino acids, glutamate or a-ketoglutarate for five hours. RNA was prepared and subjected to deep sequencing. Results: Substantial overlap was seen in the transcriptional changes in all alternative carbon sources relative to the glucose control. Source-specific changes reflected the unique metabolism of each nutrient. Conclusions: C. albicans is well-adapted to use a range of nutrients that can be found in the mammalian host and has a common transcriptional response to limiting carbon environments.
2016-11-01 | GSE87832 | GEO
Project description:Candida albicans is the most important fungal pathogen of humans, causing severe infections especially in nosocomial and immunocompromised settings. However, it is also the most prevalent fungus of the normal human microbiome, where it shares its habitat with hundreds of trillions of other microbial cells. Despite weak organic acids (WOAs) being among the most abundant metabolites produced by bacterial microbiota, little is known about their effect on C. albicans. Here we employed a sequencing-based profiling strategy to systematically investigate the transcriptional stress response of C. albicans to lactic, acetic, propionic and butyric acid at several time points after treatment. Our data reveal a complex transcriptional response, with individual WOAs triggering unique gene expression profiles and with important differences between acute and chronic exposure. In spite of all these dissimilarities, we found significant overlaps between the gene expression changes induced by each WOA, which lead us to uncover a core transcriptional signature that was unrelated to the general response to low pH. Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations. Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels in general and of ribosomal RNA in particular. In conclusion, this study suggests that GI microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its hosts in both health and disease. Transcriptional profiling of wild-type Candida albicans strain SC5314 under 6 differents condition (2 controls, 4 weak acids) at 4 time points by cDNA deep-sequencing, with 4 biological replicates, on the Illumina HiSeq 2000 platform. 96 total samples were sequenced (6 x 4 x 4).
2015-01-28 | E-GEOD-49310 | biostudies-arrayexpress
Project description:Goal of this study was to investigate the metabolic adaptation of C. albicans to different carbon sources (malic acid, α-ketoglutarate, proline) and nitrogen sources (dipeptides). As a control medium with glucose as carbon source and ammonium sulfate as nitrogen source was used. Transcriptional profiles were compared after 4 h incubation at 37°C.
2023-03-30 | GSE223317 | GEO
Project description:Candida albicans: Mig1 and Mig2 regulatory networks in YPD and YPG
| PRJNA573104 | ENA
Project description:Candida albicans is the most important fungal pathogen of humans, causing severe infections especially in nosocomial and immunocompromised settings. However, it is also the most prevalent fungus of the normal human microbiome, where it shares its habitat with hundreds of trillions of other microbial cells. Despite weak organic acids (WOAs) being among the most abundant metabolites produced by bacterial microbiota, little is known about their effect on C. albicans. Here we employed a sequencing-based profiling strategy to systematically investigate the transcriptional stress response of C. albicans to lactic, acetic, propionic and butyric acid at several time points after treatment. Our data reveal a complex transcriptional response, with individual WOAs triggering unique gene expression profiles and with important differences between acute and chronic exposure. In spite of all these dissimilarities, we found significant overlaps between the gene expression changes induced by each WOA, which lead us to uncover a core transcriptional signature that was unrelated to the general response to low pH. Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations. Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels in general and of ribosomal RNA in particular. In conclusion, this study suggests that GI microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its hosts in both health and disease.
2015-01-28 | GSE49310 | GEO
Project description:Candida albicans is a part of the normal microbiome of human mucosa and is able to thrive in a wide range of host environments. As an opportunistic pathogen, the virulence of C. albicans is tied to its ability to switch between yeast and hyphal morphologies in response to various environmental cues, one of which includes nutrient availability. Thus, metabolic flexibility plays an important role in the virulence of the pathogen. Our previous study has shown that C. albicans Yeast Casein Kinase 2 (CaYck2) regulates the yeast-to-hyphal switch, but its regulatory mechanisms remain unknown. This study further elucidated the role of Yck2 in governing morphology and carbon metabolism by analyzing the transcriptome and metabolome of the C. albicans YCK2 deletion mutant strain (yck2Δ strain) in comparison to the wild type strain. Our study revealed that loss of CaYck2 perturbs carbon metabolism, leading to a transcriptional response that resembles a transcriptional response to glucose starvation with coinciding intracellular accumulation of glucose and depletion of TCA cycle metabolites. This shift in the metabolome is likely mediated by derepression of glucose-repressed genes in the Mig1/2-mediated glucose sensing pathway and by downregulation of glycolytic genes, possibly through the Rgt1-mediated SRR pathway. In addition, genes involved in beta-oxidation, glyoxylate cycle, oxidative stress response, and arginine biosynthesis were upregulated in the yck2Δ strain, which is highly reminiscent of C. albicans engulfment by macrophages. This coincides with an increase in arginine degradation intermediates in the yck2Δ strain, suggesting arginine catabolism as a potential mechanism of CaYck2-mediated filamentation as seen during C. albicans escape from macrophages. Transcriptome analysis also shows differential expression of hyphal transcriptional regulators Nrg1 and Ume6. This suggests dysregulation of hyphal initiation and elongation in the yck2Δ strain which may lead to the constitutive pseudohyphal phenotype of this strain. Metabolome analysis also detected a high abundance of methyl citrate cycle intermediates in the yck2Δ strain, suggesting the importance of CaYck2 in this pathway. Taken together, we discovered that CaYck2 is an integral piece of carbon metabolism and morphogenesis of C. albicans.
2021-03-29 | GSE138069 | GEO
Project description:Candida albicans is a member of the normal commensal flora with the ability to cause disease in susceptible individuals. Nutrient acquisition is of central importance for C. albicans to colonize and thrive in the host. We have previously assessed the role of amino acid utilization for growth and manipulation of pH, triggering the filamentation program and promoting immune evasion. While the role of amino acids has been largely studied, protein utilization has remained less well understood. We investigated the utilization of peptides as a source of carbon and to support the neutralization phenomena. We found that both transcription factors Stp1 and Stp2 are required for proper peptide utilization in a manner dependent of amino acid sensing signaling involving the SPS system. However, we found that Stp2 is the major contributor for this process. Epistasis experiments shown that Stp1 partially restores the ability to utilize peptides in the absence of amino acid signaling, whilst Stp2 is sufficient to fully restore this phenotype. Transcriptomic analysis revealed that the response to amino acids and peptides is very similar, but peptides represent a more difficult carbon source to utilize. It is known that the Stp1/Stp2 duet has divergent roles in C. albicans, however the specific set of genes controlled by each TF remained unclear. We showed that the Stp1 regulon is limited to two oligopeptide transporters (OPT1, OPT9), and iron-acquisition oxidoreductase (CFL2), a nucleoside transporter (NUP) and a leucine aminopeptidase (APE2), whereas Stp2 is responsible for the regulation of amino acid uptake and catabolic genes, in a manner dependent of amino acid sensing. Surprisingly, Stp2 affects expression of genes involved in the filamentation response (e.g. UME6, SFL2) that have been associated with host colonization. In a GI tract competition experiment, mutants lacking the amino acid sensor Ssy1 or the TF Stp2 exhibited decreased colonization, while an stp1Δ/Δ mutant showed increase colonization. Taken together, these results highlight the importance of peptide and amino acid utilization for colonization of the host, a prerequisite for disseminated disease.
2020-02-20 | GSE145576 | GEO