Recording of DNA-binding events reveals the importance of a repurposed Candida albicans regulatory network for gut commensalism

Candida albicans is a fungal component of the human gut microbiota and an opportunistic pathogen. C. albicans transcription factors (TFs), Wort and Efg1 , are master regulators of an epigenetic switch required for fungal mating that also control colonization of the mammalian gut, We show that additional mating regulators, WOR2, WOR3, WOR4, AHR1, CZF1, and SSN6, also influence gut commensalism. Using Calling Card-seq to record Candida TF DNA-binding events in the host, we examine the role and relationships of these regulators during murine gut colonization. By comparing in-host transcriptomes of regulatory mutants with enhanced versus diminished commensal fitness, we also identify a set of candidate commensalism effectors. These include Cht2, a GPI-linked chitinase whose gene is bound by Wort, Czf1, and Efg1 in vivo, that we show promotes commensalism. Thus, the network required for a C. albicans sexual switch is biochemically active in the host intestine and repurposed to direct commensalism.

Automated summary

Candida albicans is a fungal component of the human gut microbiota and an opportunistic pathogen. In addition to known transcription factors, other mating regulators also influence gut commensalism, with some potentially serving as commensal effectors.