Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Microbiology, Pharmacology & Pharmacy, VULVO-VAGINAL CANDIDIASIS, ANTIFUNGAL AGENTS, ORAL CANDIDOSIS, FLUCONAZOLE, INFECTIONS, CHALLENGES, MANAGEMENT, MECHANISM, YEAST, Amphotericin B, Antifungal Agents, Artemisinins, Artesunate, Biofilms, Candida albicans, Candidiasis, Caspofungin, Drug Synergism, Echinocandins, Fluconazole, Hexachlorophene, Lipopeptides, Miconazole, Microbial Sensitivity Tests, Pyrvinium Compounds, Reactive Oxygen Species, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology and Pharmaceutical Sciences, 3107 Microbiology, 3207 Medical microbiology, 3214 Pharmacology and pharmaceutical sciences

Abstract:

Mucosal biofilm-related fungal infections are very common and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance against azoles (preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1600 compounds of a drug repositioning library in combination with a sub-inhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Cytotoxicity testing was performed on human foetal lung fibroblasts. Hexachlorophene, pyrvinium pamoate and artesunate act synergistically with miconazole in eradicating C. albicans biofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin or amphotericin B Miconazole-artesunate combinations show comparable cytotoxicity as miconazole alone. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treat C. albican biofilm-related infections.