title: Artemisinins, new miconazole potentiators resulting in increased activity against Candida albicans biofilms.
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.
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium Department of Plant Systems Biology, VIB, Ghent, Belgium.
authors.forename: Kaat
authors.initials: K
authors.lastname: De Cremer
authors.affiliation: Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Antwerp, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Lanckacker
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Tanne L
authors.initials: TL
authors.lastname: Cools
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Bax
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Katrijn
authors.initials: K
authors.lastname: De Brucker
authors.affiliation: Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Antwerp, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium Department of Plant Systems Biology, VIB, Ghent, Belgium Bruno.Cammue@biw.kuleuven.be.
authors.forename: Bruno P A
authors.initials: BP
authors.lastname: Cammue
authors.affiliation: Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D000077336:Caspofungin; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D006582:Hexachlorophene / Q000494:pharmacology; D055666:Lipopeptides; D008825:Miconazole / Q000494:pharmacology* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D011774:Pyrvinium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D037621:Artemisinins; D054714:Echinocandins; D055666:Lipopeptides; D011774:Pyrvinium Compounds; D017382:Reactive Oxygen Species; D000077332:Artesunate; C024631:pyrvinium; D008825:Miconazole; D000666:Amphotericin B; D015725:Fluconazole; D000077336:Caspofungin; D006582:Hexachlorophene