Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against Pseudomonas aeruginosa by Inhibiting Drug Efflux

Autor: Xiaoya Wei, Dandan Zhou, Congjuan Xu, Ping Chen, Shuiping Chen, Zhihui Cheng, Yongxin Jin, Shouguang Jin, Weihui Wu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Antibiotics, Vol 13, Iss 9, p 810 (2024)
Druh dokumentu: article
ISSN: 2079-6382
DOI: 10.3390/antibiotics13090810
Popis: Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin–ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.
Databáze: Directory of Open Access Journals
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