Characterization of Prostaglandin E2Production byCandida albicans

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Abstract
Candida albicansproduces lipid metabolites that are functionally similar to host prostaglandins. These studies, using mass spectrometry, demonstrate thatC. albicansproduces authentic prostaglandin E2(PGE2) from arachidonic acid. Maximal PGE2production was achieved at 37°C in stationary-phase culture supernatants and in cell-free lysates generated from stationary-phase cells. Interestingly, PGE2production is inhibited by both nonspecific cyclooxygenase and lipoxygenase inhibitors but not by inhibitors specific for the cyclooxygenase 2 isoenzyme. TheC. albicansgenome does not possess a cyclooxygenase homolog; however, several genes that may play a role in prostaglandin production fromC. albicanswere investigated. It was found that aC. albicansfatty acid desaturase homolog (Ole2) and a multicopper oxidase homolog (Fet3) play roles in prostaglandin production, withole2/ole2andfet3/fet3mutant strains exhibiting reduced PGE2levels compared with parent strains. This work demonstrates that the synthesis of PGE2inC. albicansproceeds via novel pathways.