Alibert Sandrine, N'gompaza Diarra Joannah, Hernandez Jessica, Stutzmann Aurélien, Fouad Marwa, Boyer Gérard, Pagès Jean-Marie
a Aix-Marseille Université, IRBA, TMCD2, UMR-MD1, Transporteurs Membranaires, Chimioresistance et Drug Design, Facultés de Médecine et de Pharmacie , Marseille , France.
b Pharmaceutical Chemistry Department, Faculty of Pharmacy , Cairo University , Giza , Egypt.
Expert Opin Drug Metab Toxicol. 2017 Mar;13(3):301-309. doi: 10.1080/17425255.2017.1251581. Epub 2016 Nov 2.
Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed. Expert opinion: Efflux pumps are new targets for the development of adjuvant in antibiotic treatments by of efflux pump inhibition. They may allow us to rejuvenate old antibiotics acting on their concentration inside the bacteria and thus potentiating their activity while blocking the release of virulence factors. It is a pharmacodynamic challenge to finalize new combined therapy.
全球已报道了令人担忧的细菌耐药水平，许多现有抗生素治疗均告失败。革兰氏阴性菌中的多重耐药性（MDR）通常归因于同一菌株中存在多种不同的耐药机制。RND外排泵起主要作用，是发现新型抗菌药物的一个有吸引力的靶点。涵盖领域：本综述讨论了外排泵的普遍性、它们在临床情况下的过表达、它们的多选择性、它们对与膜通透性改变相关的各种抗生素细胞内浓度的影响以及它们在致病性中的作用。专家观点：外排泵是通过抑制外排泵来开发抗生素治疗佐剂的新靶点。它们可能使我们能够使作用于细菌内浓度的旧抗生素恢复活力，从而增强其活性，同时阻止毒力因子的释放。确定新的联合疗法是一项药效学挑战。
