The antifungal activity of the peptide, periplanetasin-2, derived from American cockroach Periplaneta americana

The cockroach, which is a household insect, is an established model organism in research. Periplanetasin-2, derived from the American cockroach Periplaneta americana, exerted potent antifungal effect against pathogenic fungi without causing hemolysis. Periplanetasin-2 induced oxidative stress by generation of reactive oxygen species (ROS) and lipid peroxidation. Periplanetasin-2 also caused apoptosis by exposure of phosphatidylserine and fragmentation of DNA, exerted in a concentration-dependent manner. Hence, we investigated the mitochondrial apoptotic mechanism of periplanetasin-2 in Candida albicans. After treatment with periplanetasin-2, we observed mitochondrial depolarization and calcium accumulation. Moreover, we observed a decrease in cytosolic glutathione, and an increase in mitochondrial glutathione, indicating that periplanetasin-2 induced oxidative stress and high ROS production in the mitochondria. Because of this mitochondrial dysfunction, cytochrome c was released from the mitochondria into the cytosol, and caspase was activated in a time-dependent manner. In summary, the antifungal peptide periplanetasin-2 activates apoptotic signals in the mitochondria by induction of oxidative stress.