title: The transcriptional stress response of Candida albicans to weak organic acids.
abstract: 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 used 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. Despite these dissimilarities, we found significant overlaps between the gene expression changes induced by each WOA, which led us to uncover a core transcriptional response that was largely unrelated to other previously published C. albicans transcriptional stress responses. 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 and of ribosomal RNA in particular. In conclusion, this study suggests that gastrointestinal microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its host in both health and disease.
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
authors: Fabien
authors: F
authors: Cottier
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
authors: Alrina Shin Min
authors: AS
authors: Tan
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
authors: Jinmiao
authors: J
authors: Chen
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
authors: Josephine
authors: J
authors: Lum
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
authors: Francesca
authors: F
authors: Zolezzi
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors: Michael
authors: M
authors: Poidinger
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore norman_pavelka@immunol.a-star.edu.sg.
authors: Norman
authors: http://orcid.org/0000-0003-4542-9970
authors: N
authors: Pavelka
mesh_terms: D000144:Acids, Acyclic / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D012335:RNA, Ribosomal / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000144:Acids, Acyclic; D012335:RNA, Ribosomal; D019344:Lactic Acid; D012313:RNA; D007501:Iron
keywords: RNA-seq; gene expression profiling; power law global error model; short-chain fatty acid; transcriptomics
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