MIG1 regulates resistance of Candida albicans against the fungistatic effect of weak organic acids.

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MIG1 regulates resistance of Candida albicans against the fungistatic effect of weak organic acids.

Eukaryot Cell. 2015 Aug 21;

Authors: Cottier F, Tan AS, Xu X, Wang Y, Pavelka N

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-derived 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 property of WOAs on C. albicans growth and found it to occur at physiologically relevant concentrations and pH. 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 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 tested acids. Consistent with glucose being an upstream activator of Mig1p, 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 programme to fight against the fungistatic effect of this class of highly abundant metabolites produced by the GI microbiota.

PMID: 26297702 [PubMed - as supplied by publisher]