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

<i>Escherichia coli</i> (<i>E. coli</i>) 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 of <i>E. coli</i>. D-CONGA-Q7 disrupts the cell membranes of Gram-negative bacteria, and the treatment of <i>E. coli</i> strain <i>LN175</i> with D-CONGA-Q7 resulted in a significant up-regulation of the <i>Mlac</i> gene, suggesting that D-CONGA-Q7 may interact with phospholipids in the cell membrane. Furthermore, in treating <i>K88</i>-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-resistant <i>E. coli</i>.