Antibacterial Activity of a New Modified Peptide Lep5 R8-18, Derived From Scorpion Hemiscorpius lepturus Venom

Scorpion venom-derived peptides, such as those from Hemiscorpius lepturus, have gained increasing attention as potent antibacterial agents. In this study, the antibacterial activity of Lep5 R8-18, a novel scorpion venom-derived peptide generated by arginine substitution, was systematically evaluated both in vitro and in vivo, and the bactericidal mechanism was subsequently explored using FITC-labeled peptides for cellular localization assessment, membrane potential assays to evaluate depolarization, reactive oxygen species (ROS) measurements to quantify oxidative stress, and membrane integrity tests to detect permeabilization. Derived peptide Lep5 R8-18 exhibited improved antibacterial activity and reduced hemolytic activity compared with the original sequence, Lep5-18. It also reduced bacterial counts, abscess area, and inflammatory cell infiltration in mouse subcutaneous abscess models established by Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922 infection. These antibacterial effects may be mediated by depolarization of bacterial membranes, elevation of intracellular ROS levels, and disruption of membrane integrity. In conclusion, the derived peptide Lep5 R8-18 exhibits significantly enhanced antibacterial activity and markedly reduced hemolytic activity. Furthermore, its favorable in vitro and in vivo performance identifies it as a promising therapeutic candidate against S. aureus and E. coli infections.