Anti-biofilm activity of a semi-synthetic molecule obtained from resveratrol against Candida albicans biofilm

Abstract Candida albicans can form biofilm on tissues and medical devices, becoming, in that case, less susceptible to antifungal agents. Treatment of candidiasis associated with the formation of C. albicans biofilms is restricted to echinocandins and lipid forms of amphotericin B. This study investigated the activity of micafungin and resveratrol modified molecule (EB487) against C. albicans biofilms. The anti-biofilm growth (Bgrowth) and anti-preformed biofilm (Bpreformed) activities of micafungin (0 to 3.94 μM) and EB487 (0 to 20.32 mM) were comparatively studied separately and combined, using XTT, flow cytometry and cell counts approaches. Concentrations causing 50% inhibition of the studied steps (IC50) were evaluated. When tested separately, IC50 Bgrowth was obtained for 4.8 mM and 0.13 μM of EB487 and micafungin respectively, and IC50 Bpreformed for 3.6 mM and 0.06 μM of EB487 and micafungin respectively. Micafungin used alone was not able to totally eradicate fungi. Micafungin combined with EB487 displayed synergistic activity (both anti-growth- and anti-preformed biofilm-activities). Optimal combination concentrations were EB487 (≤9.12 mM -strain ATCC 28367™ or ≤8.12 mM -strain CAI4-p), micafungin (≤0.05 μM for both) and caused a total eradication of fungi. Dose reduction indexes obtained using these concentrations were at least 9 (micafungin) and 3.2 (EB487) for both anti-biofilm growth- and anti-preformed biofilm-activities. Combinations indexes were consistently below one, demonstrating a synergistic relationship between micafungin and EB487 in these conditions. This study demonstrated the strong anti-biofilm activity of EB487 and highlighted its synergistic potential when combined with micafungin. EB487 is a promising semi-synthetic molecule with prophylactic and curative interests in fighting C. albicans biofilms.