Natural product solasodine-3-O-ß-D-glucopyranoside inhibits the virulence factors of Candida albicans

Abstract

Candida albicans undergoes yeast-to-hyphal transition that has been recognized as a virulence factor as well as the key point for the development of mature biofilm. In this study, we found that a natural product, solasodine-3-O-ß-D-glucopyranoside (SG), a steroidal alkaloid glycoside, isolated from Solanum. nigrum L., could attenuate the virulence of C. albicans by inhibiting the adhesion and morphological transition. Moreover, SG dramatically inhibited the biofilm formation and displayed killing activity against the mature biofilm. In vivo study using Caenorhabditis elegans showed that SG prolonged the survival time of C. albicans infected worms. The mechanism investigation revealed that SG could inhibit the expression of adhesions and hyphae-specific genes by regulating Ras-cAMP-PKA signaling pathway. The inhibitory effects on yeast-to-hyphal conversion and biofilm formation caused by SG could be rescued by addition of exogenerous cAMP, suggesting that the retarded cAMP synthesis is responsible for these actions. Taken together, our work uncovers the underlying mechanism of SG-dependent inhibition of the yeast-to-hyphal switch and biofilm formation and provides a potential application in treating relevant fungal infections.