Anti-microbial and anti-biofilm activities of combined chelerythrine-sanguinarine and mode of action against Candida albicans and Cryptococcus neoformans in vitro

The increasing prevalence of fungal infections coupled with emerging drug resistance has stimulated an urgent need to explore new and effective antifungal agents. Sanguinarine and chelerythrine constitute alkaloids that have exhibited antifungal activities. However, the effects of a 1:1 mixture of these agents against Candida albicans and Cryptococcus neoformans have remained largely unexplored. The purpose of this study was to assess the anti-fungal and anti-biofilm efficacy of combined chelerythrine-sanguinarine against C. albicans and C. neoformans in vitro. Combined chelerythrine-sanguinarine inhibited C. albicans and C. neoformans growth with minimum inhibitory concentrations (MICs) of 2 and 16 μg/mL, respectively, and effectively inhibited adhesion and biofilm formation of these pathogens at minimum biofilm inhibitory concentrations of 1 and 8 μg/mL. Notably, the mixture significantly eradicated mature C. albicans and C. neoformans biofilms at 8 and 128 μg/mL, respectively. In particular, the mixture was found to disrupt cell membrane integrity and enhance penetration of antibiotics into fungal cells, suggesting its antifungal mode of action. Hence, combined chelerythrine-sanguinarine shows promise as a potential anti-fungal and anti-biofilm agent for the management of serious infections caused by C. albicans and C. neoformans.