The synergistic antifungal effects of gypenosides combined with fluconazole against resistant Candida albicans via inhibiting the drug efflux and biofilm formation - 27/10/20
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Highlights |
• | Gypenoside synergizes with fluconazole against planktonic cells of resistant C. albicans. |
• | Gypenoside synergizes with fluconazole against performed biofilms of C. albicans. |
• | Gypenoside enhanced in vivo efficacy of fluconazole against resistant C. albicans. |
• | The combination of gypenoside with fluconazole inhibited yeast to hyphal conversion. |
• | Gypenoside suppressed efflux pump of resistant C. albicans in a dose-dependence manner. |
Abstract |
The increased resistance of Candida to conventional antifungals brings great challenges for the clinical treatment of Candida infections. Recently, more attention has been paid to the research on combination therapy, which is a potential therapeutic approach for overcoming Candida resistance. In the present study, we first investigated the interaction between gypenosides (Gyp) and fluconazole (FLC) against Candida albicans (C. albicans) in vitro and in vivo. The in vitro test revealed a synergistic antifungal activity between Gyp and FLC against FLC-resistant (FLCR) C. albicans and indifferent effects for FLC-susceptible (FLCS) C. albicans, with the fractional inhibitory concentration index of 0.2539−0.2578 and 1–1.5, respectively. Besides, Gyp displayed synergistic interaction with FLC against FLCR C. albicans performed biofilm over 4 h, with the fractional inhibitory concentration index <0.5. In vivo, the combined antifungal efficacy of Gyp with FLC was evaluated by Galleria mellonella (G. mellonella) larvae. Gyp plus FLC prolonged the survival rate and reduced tissue invasion of larvae infected with FLCR C. albicans. Further experiments to get a first hint at what antifungal mechanisms might be inhibition of early biofilm formation, suppression of drug efflux, and inhibition of yeast-hyphal conversion. These findings will provide a new approach for the treatment of C. albicans infection.
Le texte complet de cet article est disponible en PDF.Keywords : Candida albicans, Fluconazole, Gypenosides, Galleria mellonella, Potential mechanisms, Resistance
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Vol 130
Article 110580- octobre 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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