Fungal symbionts produce prostaglandin E 2 to promote their intestinal colonization

Abstract Candida albicans is a ubiquitous fungal symbiont that resides on diverse human barrier surfaces. Both mammalian and fungal cells can convert arachidonic acid into the lipid mediator, prostaglandin E2 (PGE 2 ), but the physiological significance of fungal-derived PGE 2 remains elusive. Here we report that a C. albicans mutant deficient in PGE 2 production suffered a loss of competitive fitness in the murine gastrointestinal (GI) tract and that PGE 2 supplementation mitigated this fitness defect. Impaired fungal PGE 2 production affected neither the in vitro fitness of C. albicans nor hyphal morphogenesis and virulence in either systemic or mucosal infection models. Fungus-derived PGE 2 improved intra-GI fitness of C. albicans by diminishing the killing of C. albicans by phagocytes. Consequently, ablation of colonic phagocytes abrogated the fitness boost conferred by fungal PGE 2 . These observations suggest that C. albicans has evolved the capacity to produce PGE 2 from arachidonic acid, a host-derived precursor, to promote its own colonization of the host gut. Analogous mechanisms might undergird host-microbe interactions of other symbiont fungi. Author Summary Candida albicans is a symbiont fungus that resides in the gut of a majority of people without provoking disease. However, resident C. albicans can bloom and turn pathogenic in a subset of individuals who are immunocompromised due to infections or chemotherapy or who suffer a disruption of their intestinal microbial community due to antibiotic use. However, the fungal and host factors that regulate the fitness of C. albicans as a symbiont or an invasive pathogen remain poorly understood. Here we focused on the physiological role of fungus-derived prostaglandin E2 (PGE 2 ) in the fitness of C. albicans using a PGE 2 -deficient C. albicans strain and mouse models of infections and intestinal symbiosis. We found that fungal PGE 2 , contrary to previously described functions of promoting virulence, played no role in fungal pathogenicity in vivo . Instead, fungal PGE 2 specifically augmented the ability of C. albicans to colonize the gut, in part by reducing fungal killing by intestinal phagocytes. Our results suggest that fungal PGE 2 synthetic pathways may be prophylactically targeted in individuals susceptible to invasive infections.