Artemisinins,New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms |
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| Authors: | Kaat De Cremer Ellen Lanckacker Tanne L Cools Marijke Bax Katrijn De Brucker Paul Cos Bruno P A Cammue Karin Thevissen |
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| Institution: | aCentre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium;bDepartment of Plant Systems Biology, VIB, Ghent, Belgium;cLaboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Antwerp, Belgium |
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| Abstract: | Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affecting 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. 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. albicans biofilm-related infections. |
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