Fungal Symbionts Produce Prostaglandin E2 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 (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.

Therapeutic manipulation of gut microbiota by polysaccharides of Wolfiporia cocos reveals the contribution of the gut fungi-induced PGE2 to alcoholic hepatic steatosis

“…10 On the other hand, the production of PGE 2 by fungi is closely associated with fungal virulence and intestinal colonization. 36,37 PGE 2 was demonstrated to facilitate the growth of fungi by suppressing the interleukin-17 dependent anti-fungal immunity in mice. 38 In this work, the gut fungus M. guilliermondii enriched in mice with chronic ethanol feeding was found to produce PGE 2 on culturing with the exogenous arachidonic acid ( Figure S3), which might facilitate its intestinal colonization, and contribute to the increase of PGE 2 in the liver of AHS mice.…”

Intestinal mycobiota in health and diseases: from a disrupted equilibrium to clinical opportunities

“…Farnesol, one of the Candida-secreted quorum-sensing molecules (QSMs) [112], acts as vital virulence factor to impair the ability of immature DCs (iDC) to induce T cell differentiation and expression of pro-inflammatory cytokines, thereby, affecting pro-inflammatory and Th1 responses [85]. Notably, fungi also secrete prostaglandins (PGs) or convert exogenous arachidonic acid (AA) into PGs [103][104][105] to affect the functions of phagocytes, which contributes to continuous colonization of C. albicans [103,[106][107][108]. Moreover, fungal oxylipins are vital factors in modulating immune responses [109,110].…”

Complex and Controversial Roles of Eicosanoids in Fungal Pathogenesis

“…The production of eicosanoids by pathogenic fungi, such as C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. neoformans, H. capsulatum and A. fumigatus is linked to the pathogenesis of each fungal infection [ 4 , 9 , 51 , 60 , 64 , 65 , 66 ]. Some fungal-derived eicosanoids can enhance both fungal colonization and induce immunomodulatory effects.…”

“…However, the gut colonizing capacity of the ole2 −/− strain decreased compared to the WT strain. Besides its role in promoting colonization and survival in the mouse gut, C. albicans derived PGE 2 also inhibited fungal cell internalization by phagocytes [ 65 ]. However, in CD11b+ DC and macrophage depleted mice, the WT C. albicans strain was not able to overgrow the ole2 −/− strain [ 65 ], suggesting that the presence of PGE 2 is beneficial for fungal growth, overcoming phagocytosis, and enhancing survival within the host.…”