The Antimicrobial Peptide D-CONGA-Q7 Eradicates Drug-Resistant E. coli by Disrupting Bacterial Cell Membranes

Simple SummaryEscherichia coliis a ubiquitous pathogen, with certain strains causing severe diarrhea and intestinal illnesses, which pose significant health risks to both children and animals. As antimicrobial resistance continues to rise, traditional antibiotics are increasingly ineffective, highlighting the urgent need for novel therapeutic strategies. In this study, we investigated the antimicrobial peptide D-CONGA-Q7, aiming to evaluate its efficacy and underlying mechanism against drug-resistantE. colistrains. Our results demonstrate that D-CONGA-Q7 effectively disrupts bacterial cell membranes, leading to bacterial death, and exhibits comparable activity against polymyxin- and meropenem-resistant strains. In vivo experiments revealed that D-CONGA-Q7 significantly alleviated intestinal inflammation, reduced inflammatory cytokine levels, and promoted the repair of damaged intestinal tissues. Furthermore, D-CONGA-Q7 displayed good stability. These findings suggest that D-CONGA-Q7 not only represents a promising new approach to combat drug-resistant bacterial infections but also holds potential for clinical application.Escherichia coli(E. coli) is a zoonotic bacterium widespread in the environment, highly transmissible, and responsible for significant economic losses and millions of cases of illness annually. The rise of multidrug-resistant (MDR) strains has rendered last-line antibiotics such as polymyxin and meropenem ineffective, making the development of new antibiotics urgent. Although D-CONGA-Q7 has broad-spectrum bactericidal activity, its underlying mechanism remains poorly understood. In this study, we used in vitro and in vivo experiments to demonstrate that D-CONGA-Q7 effectively kills both antibiotic-sensitive and multidrug-resistant strains ofE. coli. D-CONGA-Q7 disrupts the cell membranes of Gram-negative bacteria, and the treatment ofE. colistrainLN175with D-CONGA-Q7 resulted in a significant up-regulation of theMlacgene, suggesting that D-CONGA-Q7 may interact with phospholipids in the cell membrane. Furthermore, in treatingK88-induced bacterial enteritis in the small intestine, D-CONGA-Q7 significantly reduced intestinal inflammation. In conclusion, this study provides a novel approach to combat drug-resistantE. coli.