Teasaponin suppresses Candida albicans filamentation by reducing the level of intracellular cAMP

Abstract

BACKGROUND: Candidiasis has long been a threat to human health, but cytotoxicity and resistance always block the usefulness of antifungal agents. The ability to switch between yeast and hypha is one of the most discussed virulence trait attributes of the human pathogenic fungus Candida albicans. The morphological transition provides a novel target for developing antifungal drugs. The aim of the present study was to explore the activity and mechanism of teasaponin (TS), a generally regarded as safe natural product, in inhibiting filamentation of C. albicans, hoping to provide an experimental basis for its clinical application. METHODS: The effect of TS on filamentation and biofilm formation of C. albicans was evaluated by XTT reduction assay and microscopy. The level of intracellular cAMP was measured to further explore the underlying mechanism. In addition, cytotoxicity of TS was evaluated by using MTT assay in vitro and Caenorhabditis elegans model in vivo. The potential of TS-resistance induction was tested by a serial passage experiment. RESULTS: TS displayed a moderate antifungal activity against the wild type, efflux pump mutant and multi-resistance C. albicans strains, and could effectively retard filamentation and biofilm formation with a low MIC value. Further mechanism investigation revealed that the reduced cAMP level inhibited filamentation and biofilm formation. In addition, TS showed no significant cytotoxicity in vitro or in vivo, and had little potential to develop resistance during long-time induction. CONCLUSIONS: Our work evaluated the antifungal activity of TS against filamentation and biofilms formation of C. albicans and disclosed the underlying mechanism, which might provide useful clues for the potential clinical application of TS in fighting clinical fungal infections by targeting the virulence factors.