Prostaglandin E2 production by Candida albicans and Candida dubliniensis

[摘要] English: Arachidonic acid (AA) [20:4(n-6)] is released from infected host cells during Candida albicans infection and may serve as carbon source for yeast growth and as precursor for the production of biologically active eicosanoids, such as prostaglandin E2 (PGE2) by C. albicans. Prostaglandin E2 is an important virulence factor in C. albicans and involved in biofilm formation. Biofilms increase damage in host cells and are more resistant to antifungal drugs than planktonic yeast cells. This study evaluated the production of prostaglandins, PGE2 and PGF2α, by biofilms of C. albicans and the closely related C. dubliniensis. Since, the mechanism involved in this production is still unclear, it was of interest to investigate the effect of different AA metabolism inhibitors on PGE2 production by biofilms of these Candida species. The experiments were done by growing Candida biofilms in the presence of AA as well as cytochrome P450 (CYP450), multicopper oxidase, cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors. The PGE2 and PGF2α concentrations were determined by a monoclonal enzyme-linked immunosorbent assay (ELISA) and verified with LCMS/MS. The results obtained indicate the ability of C. albicans and C. dubliniensis biofilms to produce PGE2 and PGF2α, from exogenous AA. The use of different inhibitors suggested that CYP450s and multicopper oxidases are involved in PGE2 production by these Candida biofilms.

[发布机构] University of the Free State