Abstract
Among ∼5,000,000 fungal species1, C. albicans is exceptional in its lifelong association with humans, either within the gastrointestinal microbiome or as an invasive pathogen2. Opportunistic infections are generally ascribed to defective host immunity3 but may require specific microbial programs. Here we report that exposure of C. albicans to the mammalian gut triggers a developmental switch, driven by the Wor1 transcription factor, to a commensal cell type. Wor1 expression was previously observed only in rare genetic backgrounds4,5,6, where it controls a white-opaque switch in mating4,5,6,7. We show that passage of wild-type cells through the mouse gastrointestinal tract triggers WOR1 expression and a novel phenotypic switch. The resulting GUT (gastrointestinally induced transition) cells differ morphologically and functionally from previously defined cell types, including opaque cells, and express a transcriptome that is optimized for the digestive tract. The white-GUT switch illuminates how a microorganism can use distinct genetic programs to transition between commensalism and invasive pathogenesis.
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Acknowledgements
We are grateful to R. Bennett for providing protocols for C. albicans scanning electron microscopy and response to mating pheromone and to A. Johnson (University of California at San Francisco) for strains and antibodies to α-Wor1. We thank S. Beyhan and M. Voorhies for guidance with BAGEL software. M. Mwangi assisted with the preparation of images of GUT and opaque cells and with colony PCR. J. Cox, H. Madhani, Q. Mitrovich and A. Sil provided helpful comments on the manuscript. This work was supported by US National Institutes of Health (NIH) grant R21AI099659-01, a University of California at San Francisco (UCSF) Program for Breakthrough Biomedical Research award, a Burroughs Wellcome Fund CABS (Career Awards in the Biomedical Sciences) award and a Pew Foundation scholarship.
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K.P. identified C. albicans mutants with altered commensal fitness, characterized the white-GUT switch and analyzed mating and pheromone response. C.C. performed strain construction, expression profiling and scanning electron microscopy. S.M.N. oversaw the work and wrote the manuscript.
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Supplementary Figures 1–7 and Supplementary Tables 1, 2 and 4–7 (PDF 3813 kb)
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Transcriptome analysis of GUT, white and opaque cells (XLSX 4305 kb)
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Pande, K., Chen, C. & Noble, S. Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. Nat Genet 45, 1088–1091 (2013). https://doi.org/10.1038/ng.2710
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DOI: https://doi.org/10.1038/ng.2710
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