The effect of Ginkgolide B combined with fluconazole against drug-resistant Candida albicans based on common resistance mechanisms.

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The effect of Ginkgolide B combined with fluconazole against drug-resistant Candida albicans based on common resistance mechanisms.

Int J Antimicrob Agents. 2020 May 23;:106030

Authors: Li Y, Yang J, Li X, Su S, Chen X, Sun S, Li Y

Abstract
The number of invasive fungal infections has dramatically increased over the recent years, leading to high morbidity and mortality of immunocompromised patients. Candida albicans (C. albicans) has been recorded as the most frequent cause of life-threatening disseminated candidiasis among invasive fungal infections. In the recent decades, the resistance of C. albicans against conventional antifungals has been frequently reported. Therefore, treatments with a combination of antifungal agents and non-antifungals are often considered to overcome drug resistance. It was shown in this study for the first time that the combination of ginkgolide B (GB) and fluconazole (FLC) could increase the sensitivity of resistant C. albicans to FLC. In vitro studies indicated that the drug combination had a synergistic effect on C. albicans both in planktonic cells and biofilms within 12h. In vivo efficacy of this drug combination was evaluated using the Galleria mellonella (G. mellonella) infection model. Survival rate, fungal burden, and histological examination were also determined. Furthermore, studies indicated that the antifungal effects of GB in combination with FLC might be associated with the inhibition of hyphal growth, disruption of intracellular calcium, and the inhibition of drug efflux pumps. The result will provide a promising solution for overcoming drug resistance of C. albicans and expanding the clinical application of existing drugs.

PMID: 32454072 [PubMed - as supplied by publisher]