Prostaglandin E(2) from Candida albicans Stimulates the Growth of Staphylococcus aureus in Mixed Biofilms

BACKGROUND: Previous studies showed that Staphylococcus aureus and Candida albicans interact synergistically in dual species biofilms resulting in enhanced mortality in animal models. METHODOLOGY/PRINCIPAL FINDINGS: The aim of the current study was to test possible candidate molecules which might mediate this synergistic interaction in an in vitro model of mixed biofilms, such as farnesol, tyrosol and prostaglandin (PG) E(2). In mono-microbial and dual biofilms of C.albicans wild type strains PGE(2) levels between 25 and 250 pg/mL were measured. Similar concentrations of purified PGE(2) significantly enhanced S.aureus biofilm formation in a mode comparable to that observed in dual species biofilms. Supernatants of the null mutant deficient in PGE(2) production did not stimulate the proliferation of S.aureus and the addition of the cyclooxygenase inhibitor indomethacin blocked the S.aureus biofilm formation in a dose-dependent manner. Additionally, S. aureus biofilm formation was boosted by low and inhibited by high farnesol concentrations. Supernatants of the farnesol-deficient C. albicans ATCC10231 strain significantly enhanced the biofilm formation of S. aureus but at a lower level than the farnesol producer SC5314. However, C. albicans ATCC10231 also produced PGE(2) but amounts were significantly lower compared to SC5314. CONCLUSION/SIGNIFICANCE: In conclision, we identified C. albicans PGE(2) as a key molecule stimulating the growth and biofilm formation of S. aureus in dual S. aureus/C. albicans biofilms, although C. albicans derived farnesol, but not tyrosol, may also contribute to this effect but to a lesser extent.