Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism

Suzanne Noble and colleagues show that the passage of Candida albicans through the mammalian gut induces expression of the Wor1 transcription factor, triggering a developmental switch that promotes commensal fitness. Among ∼5,000,000 fungal species 1 , C. albicans is exceptional in its lifelong association with humans, either within the gastrointestinal microbiome or as an invasive pathogen 2 . Opportunistic infections are generally ascribed to defective host immunity 3 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 backgrounds 4 , 5 , 6 , where it controls a white-opaque switch in mating 4 , 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.