Combination of baicalein and Amphotericin B accelerates Candida albicans apoptosis

Candida albicans is the most important human fungal pathogen. Amphotericin (AmB) is a gold standard of antifungal treatment for fungi, but the severe side effect of this drug restricts its clinical application. In this study, the interaction of AmB and baicalein (BE) was investigated against thirty clinical isolates of C. albicans. Synergistic activities were determined using the checkerboard microdilution assay based on the fractional inhibitory concentration indices. Combination of BE and AmB accelerated C. albicans apoptosis accompanied with an increase of reactive oxygen species (ROS). Moreover, AmB increased the caspase activity and expression of the corresponding gene CaMCA1 in C. albicans. These effects were enhanced in the presence of BE. Deletion of CaMCA1 clearly attenuated AmB-induced apoptosis, indicating the involvement of CaMCA1-mediated caspase pathway in AmB-induced apoptosis and the synergistic action.