喹诺酮类药物耐药机制研究进展

Advance in Resistance Mechanism of Quinolones

喹诺酮类属于合成的广谱抗菌药,用于治疗与肠杆菌科相关的各种感染性疾病。近几十年来,喹诺酮类药物的广泛使用和过度使用导致了喹诺酮耐药菌株的出现。喹诺酮类药物耐药的产生是一个复杂的多因素过程,主要的耐药机制包括染色体介导的一个或多个靶点基因突变改变靶点酶的药物结合力;AcrAB-tolC多耐药外排泵的过表达和孔蛋白的改变导致药物摄取减少,外排增加;以及质粒介导的喹诺酮类耐药基因(qnr,aac(6′)-Ib-cr和crpP)、外排泵(如OqxAB和QepA)的存在。论文通过对喹诺酮类药物耐药机制进行综述,以期为探索抗耐药菌株的新药提供参考。

Quinolones are broad-spectrum antimicrobials,which are used for the treatment of different infectious diseases associated with Enterobacteriaceae.During recent decades,the wide use as well as overuse of quinolones against diverse infections has led to the emergence of quinolone-resistant bacterial strains.The acquisition of resistance to quinolones is a complex and multifactorial process.The main resistance mechanisms consist of one or a combination of target-site gene mutations altering the drug binding affinity of target enzymes;Overexpression of AcrAB-tolC multidrug-resistant efflux pumps cause decreased drug accumulation either by increased overexpression of efflux pumps or decreased uptake,the presence of plasmid-mediated quinolone resistance(PMQR)genes including qnr,aac(6′)-Ib-cr and crpP genes,and plasmid-encoded active efflux pumps such as OqxAB and QepA.In this paper,the mechanism of quinolone resistance mechanisms was reviewed,which will help researchers to explore new drugs against the resistant strains.