Urechistachykinin I induced ferroptosis by accumulating reactive oxygen species in Vibrio vulnificus.

Abstract

Antimicrobial peptides (AMPs), such as urechistachykinin I (LRQSQFVGSR-NH2), derived from urechis unicinctus, have demonstrated antimicrobial activities. It exhibits low cytotoxicity and selectivity between microbial and mammalian cells suggesting its potent antimicrobial ability. However, the underlying antimicrobial mechanisms remain unknown. Herein, we elucidated the antibacterial action against Vibrio vulnificus, focusing on the reactive oxygen species (ROS). ROS is crucial for antibiotic-mediated killing and oxidative stress. After treatment with urechistachykinin I, superoxide anions and hydroxyl radicals increase, and the overproduction of ROS leads to oxidative damage and destruction of the redox system. Oxidation of the defense system like glutathione or glutathione peroxidase 4 illustrates the dysfunction of cellular metabolism and induces lipid peroxidation attributed to depolarization and integrity brokerage. Cell death demonstrated these properties, and additional experiments, including iron accumulation, liperfluo, and DNA fragmentation, were promoted. The results demonstrated that urechistachykinin I-induced ferroptosis-like death in Vibrio vulnificus is dependent on ROS production. KEY POINTS: •Urechistachykinin I induce reactive oxygen species production •Urechistachykinin I cause oxidative damaged on the V. vulnificus •Urechistachykinin I ferroptosis-like death in V. vulnificus.