Aloin remodels the cell wall of Candida albicans to reduce its hyphal virulence against oral candidiasis.

Aloe vera (L.) Burm.f. is a traditional Chinese medicine known for treating various ailments, including fungal infections. Aloin is one of the major components from A. vera, but its antifungal mechanism and therapeutic potential against oral candidiasis are not clear. This study aimed to examine the mechanism of aloin against Candida albicans and its inhibitory activity against oral candidiasis. In this study, we for the first time found that aloin could induce the formation of abnormal hyphae with smaller hyphal diameters and fewer branching points in C. albicans including 11 clinical isolates without growth inhibition. The transcriptome and further cell wall contents analysis indicated that aloin remodeled the cell wall to increase the contents of β-1,3-glucan and furtherly showed an antagonistic effect with micafungin. Aloin also significantly inhibited the cell damage of oral epithelial cells and oral candidiasis in mice infected by C. albicans due to its inhibitory actions on the hyphal development and expressions of virulence factors, including candidalysin (coded by ECE1). Our results suggest that aloin is a promising antifungal agent for controlling candidiasis and targeting hyphal development and pathogenesis represents a practical strategy for developing new antifungal drugs. KEY POINTS: • Aloin remodels the C. albicans cell wall to form avirulent hyphae. • Aloin inhibits C. albicans infections in oral epithelial cells and mouse mucosa without toxicity. • Aloin is a promising antifungal agent with therapeutic potential against C. albicans infections.