Antibacterial efficacy and mechanism of Cyprinus carpio chemokine-derived L-10 against multidrug-resistant Escherichia coli infections

Objectives Antimicrobial resistance has raised concerns regarding untreatable infections and poses a growing threat to public health. Rational design of new AMPs is an ideal solution to this threat. Methods In this study, we designed, modified, and synthesised an excellent AMP, L -10, based on the original sequence of the Cyprinus carpio chemokine. All experimental data were presented as the mean ± standard deviation (SD), and the two-tailed unpaired T-test method was used to analyze all data. Results L-10 exhibited excellent antibacterial activity with negligible toxicity and improved the efficacy of a broad class of antibiotics against MDR Gram-negative pathogens, including tetracycline, meropenem, levofloxacin, and rifampin. Mechanistic studies have suggested that L -10 targets the bacterial membrane components, LPS and PG, to disrupt bacterial membrane integrity, thereby exerting antibacterial effects and enhancing the efficacy of antibiotics. Moreover, in animal infection models, L -10 significantly increased the survival rate of infected animals and effectively reduced the tissue bacterial load and inflammatory factor levels. In addition to its direct antibacterial activity, L -10 dramatically reduced pulmonary pathological alterations in a mouse model of endotoxemia and suppressed LPS-induced proinflammatory cytokines in vitro and in vivo . Lastly, L -10 was successfully expressed in Pichia pastoris and maintained antimicrobial activity against MDR Gram-negative pathogens in vivo and in vitro . Conclusion Collectively, these results reveal the potential of L -10 as an ideal candidate against MDR bacterial infections and provide new insights into the design, development, and clinical application of AMPs.

文章引用产品列表