A novel peptide mR63-77 from Rpl36 protein showing potent antibacterial activities.

The abuse and overuse of antibiotics have triggered a global antibiotic resistance crisis, posing a severe threat to human public health security. Thus, the development of highly efficient and human-safe antibiotic alternatives is imminent. Here, we demonstrated that Rpl36 in zebrafish possessed antibacterial properties and was capable of interacting with peptidoglycan. Based on this finding, four candidate peptides were screened from the protein sequence, and their antibacterial potential was systematically evaluated. The results showed that mR63-77 exhibited robust antibacterial activity, along with favourable thermal stability and acid resistance, indicating its great potential for development as an antibacterial peptide. Furthermore, scanning electron microscope assays, bacterial membrane depolarization assays, and outer membrane permeabilization assays confirmed that mR63-77 exerted direct bactericidal effects by disrupting the bacterial cell membrane. Importantly, mR63-77 showed no hemolysis to red blood cells. In vivo experiments revealed that mR63-77 could effectively alleviate the inflammatory response and oxidative stress injury in zebrafish infected with S. aureus; in female mouse models with S. aureus-infected skin wounds, mR63-77 efficiently inhibited wound infection, accelerated skin tissue repair, and caused no obvious toxicity to major organs. Taken together, the antibacterial peptide mR63-77 integrated excellent antibacterial activity, desirable stability, and high biosecurity, holding substantial translational potential for the treatment of drugresistant bacterial infections.