Self-assembling anti-Gram-negative bacterial peptide derivatives with potent broad-spectrum antimicrobial activity
Hongyan Yang, Lan Wang, Fei Pan, Libo Yuan, Heng Du, Pei Zhang, Kui Lu
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.