Murepavadin promotes the killing efficacies of aminoglycoside antibiotics against <i>Pseudomonas aeruginosa</i> by enhancing membrane potential
Xiaoya Wei, Jiacong Gao, Dan-Dan Zhou, Congjuan Xu, Ping Chen, Shuiping Chen, Yanhong Zhang, Xuehua Liu, Guanxian Li, Guangbo Zhu, Huimin Liu, Jinjin Li, Bin Geng, Linlin Gao, Zhihui Cheng, Iain L. Lamont, Daniel Pletzer, Yongxin Jin, Shouguang Jin, Weihui Wu
Abstract
ABSTRACT Murepavadin is a peptidomimetic that specifically targets the lipopolysaccharide transport protein LptD of Pseudomonas aeruginosa . Here, we found that murepavadin enhances the bactericidal efficacies of tobramycin and amikacin. We further demonstrated that murepavadin enhances bacterial respiration activity and subsequent membrane potential, which promotes intracellular uptake of aminoglycoside antibiotics. In addition, the murepavadin-amikacin combination displayed a synergistic bactericidal effect in a murine pneumonia model.