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 (PGE2), but the physiological significance of fungus-derived PGE2 remains elusive. Here we report that a C. albicans mutant deficient in PGE2 production suffered a loss of competitive fitness in the murine gastrointestinal (GI) tract and that PGE2 supplementation mitigated this fitness defect. Impaired fungal PGE2 production affected neither the in vitro fitness of C. albicans nor hyphal morphogenesis and virulence in either systemic or mucosal infection models. Instead, fungal production of PGE2 was associated with enhanced fungal survival within phagocytes. Consequently, ablation of colonic phagocytes abrogated the intra-GI fitness boost conferred by fungal PGE2. These observations suggest that C. albicans has evolved the capacity to produce PGE2 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.
Highlights
Candida albicans is one of the most successful fungal symbionts in humans, colonizing 40–80% of individuals in industrialized nations and typically representing the predominant species within the fungal microbiota (Odds, 1987; MacCallum, 2010)
We measured in vitro prostaglandin E2 (PGE2) production across an array of symbiont fungi and confirmed that all species tested, including Saccharomyces cerevisiae, secreted PGE2 when supplied with exogenous arachidonic acid (AA) (Figure 1A), implying a PGE2 biosynthetic pathway conserved across the majority of fungal species
We sought a C. albicans mutant with altered PGE2 production which we could use to study the physiological function of fungus-derived PGE2
Summary
Candida albicans is one of the most successful fungal symbionts in humans, colonizing 40–80% of individuals in industrialized nations and typically representing the predominant species within the fungal microbiota (Odds, 1987; MacCallum, 2010). C. albicans dwells on diverse barrier sites of the body, including the oral cavity, skin, female reproductive tract, and the intestines, where it does not cause symptomatic disease (Odds, 1987; MacCallum, 2010). C. albicans can turn pathogenic and result in mucosal or life-threatening invasive bloodstream infections under a variety of conditions that compromise host immunity, damage barrier surfaces, or disrupt the microbiota (Brown et al, 2012; Fan et al, 2015). In turn, restricted by the host immune system
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