Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against <i>Pseudomonas aeruginosa</i> by Inhibiting Drug Efflux
Xiaoya Wei,
Dandan Zhou,
Congjuan Xu,
Ping Chen,
Shuiping Chen,
Zhihui Cheng,
Yongxin Jin,
Shouguang Jin,
Weihui Wu
Affiliations
Xiaoya Wei
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Dandan Zhou
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Congjuan Xu
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Ping Chen
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Shuiping Chen
Department of Laboratory Medicine, 5th Medical Center of PLA General Hospital, Beijing 100071, China
Zhihui Cheng
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Yongxin Jin
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Shouguang Jin
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Weihui Wu
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
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.
