Scolopendin, an antimicrobial peptide from centipede, attenuates mitochondrial functions and triggers apoptosis in Candida albicans

Abstract

Centipedes, a type of arthropod, reportedly produce antimicrobial peptides as part of an innate immune response. Scolopendin (SPSEKAGLQPVGRIGRMLKK) is a novel antimicrobial peptide derived from Scolopendra subspinipes mutilans. Many antifungal agents have more than one type of cell death mechanism. Although scolopendin is involved in membrane perturbation, the corresponding intracellular changes require further investigation. Therefore, we assessed the cell morphology and calcium ion concentration of the cytosol and mitochondria of scolopendin-treated cells. The treated cells were shrunken, and calcium ion homeostasis was disrupted in both the cytosol and mitochondria. These conditions attenuated mitochondrial homeostasis, disrupting mitochondrial membrane potential and cytochrome c levels. Fungal cells treated with scolopendin exhibited various apoptotic phenotypes such as reactive oxygen species accumulation, phosphatidylserine exposure, chromatin condensation, and nuclear fragmentation. Scolopendin-induced cell death also triggered metacaspase activation. In conclusion, treatment of Candida albicans with scolopendin induced the apoptotic response, which in turn led to mitochondrial dysfunction, metacaspase activation, and cell death. The antimicrobial peptide scolopendin from the centipede S.s. mutilans demonstrated a novel apoptotic mechanism as an antifungal agent.