Phosphate is the third nutrient monitored by TOR in Candida albicans and provides a target for fungal-specific indirect TOR inhibition

Significance The human fungal pathogen Candida albicans uses the Target of Rapamycin (TOR) signaling pathway to contend with varying host environments and thereby, regulate cell growth. Seeking unknown components of the C. albicans TOR pathway, we identified a phosphate importer, Pho84, and its molecular link to Target of Rapamycin complex 1 (TORC1). Because phosphorus is a critical element for anabolic processes, like DNA replication, ribosome biogenesis, translation, and membrane biosynthesis, TORC1 monitors its availability in regulating these processes. By depleting the central kinase in the TORC1 pathway, we showed that TORC1 signaling modulates regulation of phosphate acquisition. A Food and Drug Administration-approved small molecule inhibitor of Pho84 inhibits TORC1 signaling and potentiates the activity of the antifungals amphotericin B and micafungin.