Shown are the mean cfu and the standard deviations of two independent experiments each with three replicates

Asterisks reveal statistically important variances (pEpidemiology and determinants exclusively linked with exacerbations that call for healthcare facility admission have been significantly less thoroughly explained biofilms (Figs 4A and 5A). To test the hypothesis that PGE2 is responsible for the stimulatory effect of C. albicans on S. aureus biofilms, the effect of cell-free supernatants derived from PGE2 producers (C. albicans SC5314 and C. albicans ura3-/-) and from the PGE2 nonproducer (C. albicans ura3-/-fet31-/-) to the growth of S. aureus was investigated (Fig 5B). Supernatants derived from the PGE2-deficient mutant were unable to stimulate the growth of S. aureus. Interestingly, the farnesol producer C. albicans SC5314 secreted significantly higher levels of PGE2 than the farnesol-deficient strain ATCC10231 (Fig 5C).In addition, we tested whether the nonspecific cyclooxygenase inhibitor indomethacin can influences the stimulatory activity of C. albicans to S. aureus. Indomethacin at a concentration between 10 and 1000 pg/mL efficiently blocked the biosynthesis of PGE2 (Fig 6A) and its metabolites (Fig 6B) by C. albicans. In cultures of mixed S. aureus/C. albicans biofilms indomethacin significantly suppressed the growth of S. aureus in a dose-dependent manner (Fig 6C). Experiments performed with the S. aureus small colony variant 31338 revealed similar results. Neither DMSO nor Indomethacin significantly affected the growth of S. aureus or C. albicans. Data are exemplarily represented for S. aureus 19552 and C. albicans SC5314 (S3 Fig).Fig 3. Effect of farnesol on the growth of S. aureus 19552 in mono-microbial biofilms. (a) Pre-cultered 24h old S. aureus biofilms were supplemented with different concentrations of purified farnesol and the number of cfu`s was determined. S. aureus biofilms incubated in farnesol-free medium were used as control. (b) Growth kinetics of S. aureus in dual biofilms with the farnesol-deficient C. albicans strain ATCC10231 (striped) and the farnesol producer C. albicans SC5314 (open bars). Colony forming units (cfu`s) of S. aureus derived from single species biofilms were function as control (solid bars).