The discovery of novel antimicrobial peptides against drug-resistant bacteria based on fragments fusion strategy.

Since the escalating prevalence of multidrug-resistant (MDR) bacterial infections posing global health challenges, novel antimicrobial agents are urgently needed. This study designed a series of antimicrobial peptides by fusing two fragments of antimicrobial peptides sC184b (1-9) and MSI-78 (10-16). Among these peptides, 13DKallDab exhibited broad-spectrum antimicrobial efficacy against six different MDR bacterial strains with relatively low MICs. It exerted antibacterial effects through a membrane-disruption mechanism and maintained high stability in serum environment. Moreover, 13DKallDab displayed low cytotoxicity and hemolysis in vitro, and significant therapeutic efficacy in a mouse acute peritonitis model. These findings demonstrate that 13DKallDab is a promising antimicrobial agent in counteracting multidrug-resistant bacterial infections.