S6.3d Candida albicans commensalism in the oral mucosa is favored by limited virulence and metabolic adaptation

S6.3 FUNGAL ADAPTATION AND EVOLUTION, SEPTEMBER 22, 2022, 4:45 PM - 6:15 PM: OBJECTIVES: As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces. Commensalism is tightly controlled by complex fungus-host interactions that preclude fungal elimination but also fungal overgrowth and invasion that would result in disease. As such, defects in antifungal T cell immunity render individuals susceptible to oral thrush due to interrupted immunosurveillance. The factors that promote commensalism and ensure persistence of C. albicans in a fully immunocompetent host remain less clear. In this study, we aimed at identifying determinants of C. albicans commensalism in the oral cavity. METHODS: We used an experimental model of C. albicans oral colonization in mice, profiled the transcriptome of the fungus in the mucosal tissue, and conducted functional studies with the prototypical commensal isolate 101 in host-free and host-involving conditions. RESULTS: C. albicans commensalism is associated with a characteristic metabolic profile tailored to the nutrient-poor conditions in the stratum corneum of the epithelium where the fungus resides. Metabolic adaptation of the commensal isolate 101 was also reflected in enhanced nutrient acquisition when grown on oral mucosa substrates. Persistent colonization of the oral mucosa by C. albicans also correlated inversely with the capacity of the fungus to induce epithelial cell damage and to elicit an inflammatory response. These immune evasive properties of isolate 101 are explained by a strong attenuation of numerous virulence genes, including those linked to filamentation. De-repression of the hyphal program by deletion or conditional repression of the transcriptional repressor NRG1 abolished the commensal behavior of isolate 101. CONCLUSIONS: This study establishes a central role of NRG1 in the commensal lifestyle of C. albicans in the oral niche of the host.