Fungal commensalism modulated by a dual-action phosphate transceptor.

Successful host colonization by fungi in fluctuating niches requires response and adaptation to multiple environmental stresses. However, our understanding about how fungal species thrive in the gastrointestinal (GI) ecosystem by combing multifaceted nutritional stress with respect to homeostatic host-commensal interactions is still in its infancy. Here, we discover that depletion of the phosphate transceptor Pho84 across multiple fungal species encountered a substantial cost in gastrointestinal colonization. Mechanistically, Pho84 enhances the gastrointestinal commensalism via a dual-action activity, coordinating both phosphate uptake and TOR activation by induction of the transcriptional regulator Try4 and downstream commensalism-related transcription. As such, Pho84 promotes Candida albicans commensalism, but this does not translate into enhanced pathogenicity. Thus, our study uncovers a specific nutrient-dependent dual-action regulatory pathway for Pho84 on fungal commensalism.