The novel antifungal agent AB-22 displays in vitro activity against hyphal growth and biofilm formation in Candida albicans and potency for treating systemic candidiasis.

Abstract

Systemic candidiasis, which is mainly caused by Candida albicans, is a serious acute fungal infection in the clinical setting. In a previous study, we reported that compound 22h (designated as AB-22 in this study), a vinyl sulfate compound, is a fast-acting fungicidal agent against a broad spectrum of fungal pathogens. In this study, we aimed to further analyze the in vitro and in vivo efficacy of AB-22 against filamentation, biofilm formation, and virulence of C. albicans. Under in vitro hyphal growth-inducing condition, AB-22 effectively inhibited germ tube formation and hyphal growth, which are required for the initiation of biofilm formation. Indeed, AB-22 significantly suppressed C. albicans biofilm formation in a dose-dependent manner. Moreover, AB-22 treatment inhibited the normal induction of ALS3, HWP1, and ECE1, which are all required for hyphal transition in C. albicans. Furthermore, AB-22 treatment increased the survival of mice systemically infected with C. albicans. In conclusion, in addition to its fungicidal activity, AB-22 inhibits filamentation and biofilm formation in C. albicans, which could collectively contribute to its potent in vivo efficacy against systemic candidiasis.