Optimal Design, Antimicrobial Activity and Action Mechanisms of an Antimicrobial Peptide Derived from Rainbow Trout Hepcidin

Abstract

Bacterial resistance is a growing worldwide concern, making the development of antimicrobial drugs with new action mechanisms to be an urgent need. Based on the relationship between the structure of antimicrobial peptides and antimicrobial activity, the mature antimicrobial peptide Hepcidin of rainbow trout was modified by amino acid substitution and designated as QS25 and other three polypeptides LS25, IS25 and QK25 were optimized based on QS25, then the four polypeptides were synthesized. The optimized polypeptide QK25 showed broader antibacterial spectrum and better antibacterial activity than that of other polypeptides. The minimum inhibitory concentration of QK25 against Staphylococcus aureus and Klebsiella pneumoniae was 62.5 ?g/mL. A large number of proteins and nucleic acids were detected in the bacterial solution after QK25 incubation for 8h. QK25 could destroy the integrity of bacterial cell membranes confirmed by SEM. The four polypeptides bind to DNA and neutralize LPS. In this study, the relationship between the structure of antimicrobial peptides and antimicrobial activity was optimized, and three Hepcidin-derived peptides with stronger antimicrobial activity and broader antibacterial spectrum were obtained. This study could provide a reference and basis for the optimal design of antimicrobial peptides.