Dataset Information

MIG1 Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids.

ABSTRACT: Candida albicans is the leading cause of fungal infections; but it is also a member of the human microbiome, an ecosystem of thousands of microbial species potentially influencing the outcome of host-fungal interactions. Accordingly, antibacterial therapy raises the risk of candidiasis, yet the underlying mechanism is currently not fully understood. We hypothesize the existence of bacterial metabolites that normally control C. albicans growth and of fungal resistance mechanisms against these metabolites. Among the most abundant microbiota-derived metabolites found on human mucosal surfaces are weak organic acids (WOAs), such as acetic, propionic, butyric, and lactic acid. Here, we used quantitative growth assays to investigate the dose-dependent fungistatic properties of WOAs on C. albicans growth and found inhibition of growth to occur at physiologically relevant concentrations and pH values. This effect was conserved across distantly related fungal species both inside and outside the CTG clade. We next screened a library of transcription factor mutants and identified several genes required for the resistance of C. albicans to one or more WOAs. A single gene, MIG1, previously known for its role in glucose repression, conferred resistance against all four acids tested. Consistent with glucose being an upstream activator of Mig1p, the presence of this carbon source was required for WOA resistance in wild-type C. albicans. Conversely, a MIG1-complemented strain completely restored the glucose-dependent resistance against WOAs. We conclude that Mig1p plays a central role in orchestrating a transcriptional program to fight against the fungistatic effect of this class of highly abundant metabolites produced by the gastrointestinal tract microbiota.

SUBMITTER: Cottier F

PROVIDER: S-EPMC4588629 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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MIG1 Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids.

Cottier Fabien F Tan Alrina Shin Min AS Xu Xiaoli X Wang Yue Y Pavelka Norman N

Eukaryotic cell 20150821 10

Candida albicans is the leading cause of fungal infections; but it is also a member of the human microbiome, an ecosystem of thousands of microbial species potentially influencing the outcome of host-fungal interactions. Accordingly, antibacterial therapy raises the risk of candidiasis, yet the underlying mechanism is currently not fully understood. We hypothesize the existence of bacterial metabolites that normally control C. albicans growth and of fungal resistance mechanisms against these met ...[more]

PMID: 26297702

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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).

Dataset Information

MIG1 Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids.

Publications

MIG1 Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids.

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