Fungal symbionts produce prostaglandin E2to promote their intestinal colonization

Abstract

AbstractCandida albicansis 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 (PGE2), but the physiological significance of fungal-derived PGE2remains elusive. Here we report that aC. albicansmutant deficient in PGE2production suffered a loss of competitive fitness in the murine gastrointestinal (GI) tract and that PGE2supplementation mitigated this fitness defect. Impaired fungal PGE2production affected neither thein vitrofitness ofC. albicansnor hyphal morphogenesis and virulence in either systemic or mucosal infection models. Fungus-derived PGE2improved intra-GI fitness ofC. albicansby diminishing the killing ofC. albicansby phagocytes. Consequently, ablation of colonic phagocytes abrogated the fitness boost conferred by fungal PGE2. These observations suggest thatC. albicanshas evolved the capacity to produce PGE2from 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 SummaryCandida albicansis a symbiont fungus that resides in the gut of a majority of people without provoking disease. However, residentC. albicanscan 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 ofC. albicansas a symbiont or an invasive pathogen remain poorly understood. Here we focused on the physiological role of fungus-derived prostaglandin E2 (PGE2) in the fitness ofC. albicansusing a PGE2-deficientC. albicansstrain and mouse models of infections and intestinal symbiosis. We found that fungal PGE2, contrary to previously described functions of promoting virulence, played no role in fungal pathogenicityin vivo. Instead, fungal PGE2specifically augmented the ability ofC. albicansto colonize the gut, in part by reducing fungal killing by intestinal phagocytes. Our results suggest that fungal PGE2synthetic pathways may be prophylactically targeted in individuals susceptible to invasive infections.