Melittin triggers apoptosis in Candida albicans through the reactive oxygen species-mediated mitochondria/caspase-dependent pathway

Melittin is one of the best-studied antimicrobial peptides, and many studies have focused on the membrane underlying its membrane-disruptive activity. We previously showed that melittin could cause some hallmarks of apoptosis in Candida albicans. Here, we first report the exact mechanism of melittin-induced fungal apoptosis. We first characterized the reactive oxygen species generated by melittin. The results showed that melittin strongly produced highly reactive hydroxyl radicals (̇OH), which contribute to cell death. Next, we showed that melittin also disrupted the mitochondrial membrane potential (ΔΨm) and induced the Ca²⁺ release from the endoplasmic reticulum and its remarkable accumulation in mitochondria. Finally, we investigated the role of caspase in the apoptotic pathway. The results showed that melittin activated metacaspase, which was mediated by cytochrome c release. To summarize, melittin is involved in the mitochondria- and caspase-dependent apoptotic pathway in C. albicans. Our findings suggest that melittin possesses a dual antimicrobial mechanism, including membrane-disruptive and apoptotic actions. The antimicrobial honeybee venome peptide melittin has two modes of action against Candida albicans.