Bat-Derived Antimicrobial Peptide MC-CATH3 Confers Protection Against Bacterial Infections via a Potential Ferroptosis-Like Death Process.

Most naturally occurring antimicrobial peptides (AMPs) exert bactericidal activity by disrupting bacterial membranes, and although alternative mechanisms have been described, AMPs associated with ferroptosis-like features in bacterial killing remain rare. Here, we identified three novel AMPs, MC-CATH1-3, from the bat Myotis chinensis. All three peptides adopt an α-helical conformation and display potent antimicrobial activity. Notably, compared with MC-CATH1/2, MC-CATH3 causes weak membrane perturbation but triggers metabolic imbalance and excessive production of reactive oxygen species, accompanied by iron-sulfur cluster damage and abnormal intracellular Fe2+ accumulation. These events are associated with Fenton reaction-driven lipid peroxidation and are consistent with a potential ferroptosis-like bacterial death process. In vivo, MC-CATHs, especially MC-CATH3, exhibit remarkable therapeutic efficacy in cutaneous wound infection. Collectively, our findings broaden the conceptual framework of AMP mechanisms and suggest that MC-CATH3 may serve as a promising template for the rational design of peptide antibiotics with novel modes of action.