Virtual screening and biological activity evaluation of novel efflux pump inhibitors targeting RE-CmeB in Campylobacter spp.

Abstract RE-CmeABC is a variant of the efflux pump CmeABC in the major zoonotic pathogen Campylobacter , which is much more potent in conferring resistance to various antibiotics for the treatment of Campylobacter infections in both veterinary and medical clinics. This potent multidrug efflux pump RE-CmeABC is widely distributed and disseminated around the world, posing a serious threat to public health. In this study, we targeted the key efflux protein RE-CmeB of RE-CmeABC to explore promising efflux pump inhibitors derived from natural products to improve the multidrug resistance of Campylobacter. We constructed a protein screening model and utilized virtual screening techniques, such as molecular docking, to identify potential efflux pump inhibitors from natural product databases. The activity and safety of these candidates were subsequently evaluated, and ZINC338037 was shown to inhibit antibiotic extrusion and restore the susceptibility of multidrug-resistant Campylobacter . In summary, a potential multidrug efflux pump inhibitor was identified and is expected to be developed as an adjuvant drug for the treatment of clinical infections caused by multidrug-resistant Campylobacter .