The role of OLE2 and POX1-3 in prostaglandin E2 production and virulence is conserved in Candidozyma (Candida) auris.

UNLABELLED: Lipids have recently gained attention for their involvement in the virulence of pathogenic yeast. One group of lipids, prostaglandins, which are arachidonic acid-derived eicosanoids, has received particular attention. Prostaglandin E2 (PGE2) is the most studied prostaglandin in mammals. However, pathogenic yeast, including Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida dubliniensis, also produces PGE2. Notably, PGE2 production has not yet been reported in Candidozyma auris (Candida auris). In C. albicans, PGE2 plays a crucial role in colonization and virulence by promoting yeast-to-hyphal transition, enhancing biofilm formation and colonization of the gastrointestinal tract. Although the biochemical pathway responsible for PGE2 synthesis in yeasts is unknown, several genes have been implicated, including OLE2 and POX1-3, which were investigated in this study. Deletion mutants of these genes were generated using a CRISPR-Cas9 system, and the production of PGE2 by the mutants was quantified using enzyme-linked immunosorbent assay and confirmed using liquid chromatography-tandem mass spectrometry. Furthermore, the involvement of these genes in virulence was assessed using a survival assay in Caenorhabditis elegans. This study presents the first report of PGE2 production by C. auris, and it demonstrates that OLE2 and POX1-3 play significant roles in PGE2 production and virulence of this yeast in C. elegans. Additionally, deletion of OLE2 in C. auris led to an accumulation of monounsaturated fatty acids, providing evidence that OLE2 does not encode a Δ9 desaturase. The conserved nature of the PGE2 production and virulence requirements among different pathogenic yeasts indicates the potential for broad-spectrum drug targeting.

IMPORTANCE

This study reveals, for the first time, that Candidozyma (Candida auris)-a growing global health threat, often causing outbreaks in hospitals-can produce a prostaglandin E2 (PGE2), which is known to influence how the immune system responds and has been linked to increased virulence in other yeast species. By identifying specific genes (OLE2 and POX1-3) involved in PGE2 production and virulence, potential novel drug targets have been identified. Understanding how C. auris produces PGE2 and how this contributes to its ability to infect and survive in hosts could lead to innovative therapies that block these pathways, making infections easier to treat.