Two novel antimicrobial peptides P_33-57 and mP_168-187 from zebrafish showing potent antibacterial activities

It is known that overuse or abuse of antibiotics has undoubtedly accelerated the global antibiotic resistance crisis, and long-time use of antibiotics may have adverse effects on the health of animal, human, and ecosystem. Therefore, it is necessary to find antibiotic alternatives that can be used in aquaculture and are non-toxic to the human. Here we clearly demonstrated that both the PH and FYVE domain of Plekhf2 in zebrafish have antibacterial properties and can interact with PGN in this study. Therefore, we screened four candidate peptides from the two domains. It was demonstrated that P_152-172 and P_168-187 had no obvious antibacterial activities, while P_33-57 and mP_168-187 had strong antibacterial activities, which may be used as antimicrobial peptides. Additionally, transmission electron microscopy experiment revealed that P_33-57 and mP_168-187 can destroy the cell wall of bacteria, thereby directly killing bacteria. Importantly, it was found that P_33-57 and mP_168-187 had no hemolysis to red blood cells and lacked cytotoxicity. In summary, P_33-57 and mP_168-187could be seen as antibacterial activity centers of PLEKHF2 and may be promising antimicrobial peptides to combat bacterial infections facing an antibiotic-resistance crisis.