Characterization of the first antimicrobial peptide from Sea Seal with potent therapeutic effect in septic mice

Marine organisms are a valuable source of natural bioactive substances, and an increasing number of marine antimicrobial peptides as the potential alternative to antibiotics are being developed. Nonetheless, antimicrobial peptides from Antarctic mammals have not been reported heretofore. In this context, we identified a Cathelicidin antimicrobial peptide, Cath-LW (RLRDLIRRGRQKIGRRINRLGRRIQDILKNLQPGKVS), from the whole-genome database of Leptonychotes weddellii, an Antarctic mammal. Cath-LW was characterized to exhibit a typical α-helix structure and broad-spectrum antimicrobial activity. Furthermore, Cath-LW was found to exert its antibacterial effect by destroying cytomembrane, binding to bacterial genome, and inhibiting DNA function. Additionally, Cath-LW could neutralize lipopolysaccharide (LPS) and inhibit LPS-induced inflammatory responses. Interestingly, Cath-LW also showed anticoagulant activity and suppressed FeCl₃-induced carotid thrombosis in mice. Finally, in septic mice, Cath-LW was demonstrated to improve the survival rate by effectively alleviating organ inflammation and damage, as well as thrombus formation. These findings not only deepen our understanding of the survival strategies of L. weddellii against microbial infections but also provide a crucial template for developing a novel multifunctional anti-sepsis drug.