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

Abstract

The number of invasive fungal infections has increased dramatically over recent years, leading to high morbidity and mortality of immunocompromised patients. Candida albicans is the most common cause of life-threatening disseminated candidiasis among invasive fungal infections. Resistance of C. albicans against conventional antifungals is frequently reported. Treatment with a combination of antifungal and non-antifungal agents is often considered in the aim to overcome drug resistance. This study shows for the first time that the combination of ginkgolide B (GB) and fluconazole (FLC) increases the sensitivity of resistant C. albicans to FLC. In vitro studies indicated that the drug combination had a synergistic effect on C. albicans in both planktonic cells and biofilms within 12 h. In vivo efficacy of this drug combination was evaluated using the Galleria mellonella infection model. Survival rate, fungal burden, and histological examination were determined. Studies indicated that the antifungal effects of GB in combination with FLC might be associated with inhibition of hyphal growth, disruption of intracellular calcium, and inhibition of drug efflux pumps. The results indicate a promising solution for overcoming drug resistance of C. albicans and expanding the clinical application of existing drugs.