Self-assembling anti-Gram-negative bacterial peptide derivatives with potent broad-spectrum antimicrobial activity

Abstract

Food contamination caused by bacteria is an important challenge in the food industry. In this study, the peptide derivative C12−CL5 was produced by attaching a 12-carbon saturated fatty acid to the N-terminus of the anti-Gram-negative bacterial peptide CL5. The amphiphilic lipopeptide C12−CL5 self-assembled into core-shell nanostructures at concentrations above its critical aggregation concentration. It was found that the self-assembling C12−CL5 showed potent activity against both Gram-negative and Gram-positive bacteria, with minimum inhibitory concentrations of 4–32 μM. Moreover, C12−CL5 exhibited good thermal stability, excellent salt tolerance, as well as strong and rapid killing kinetics. Studies on the antimicrobial mechanism of C12−CL5 indicated that it could disrupt cell membranes, leading to leakage of cellular contents and ultimately to bacterial death. This study revealed that the self-assembly of antimicrobial peptides improved their antimicrobial activity and spectrum. It provides the insights and basis for the development of potent and broad-spectrum antimicrobial peptides for use, e.g., in the food industry.