Antibacterial efficacy and mechanism of Cyprinus carpio chemokine-derived L-10 against multidrug-resistant Escherichia coli infections.
Int J Antimicrob Agents
; 63(4): 107104, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38325720
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carpas
/
Infecciones por Escherichia coli
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Antimicrob Agents
Año:
2024
Tipo del documento:
Article
País de afiliación:
China