喹诺酮类药物的抗菌和抗性机制

Antibacterial and resistant mechanisms of quinolones

关键词:  喹诺酮  抗菌机制  细菌  抗性机制

Key words:  quinolones  antibacterial mechanisms  bacteria  resistance mechanisms

摘要:

喹诺酮类药物是广泛使用的一类抗菌药物,日趋严峻的细菌耐药性已严重威胁其临床应用。介绍喹诺酮类药物的发展过程,其靶向细菌DNA促旋酶和拓扑异构酶Ⅳ抑制DNA复制的抗菌机制,并进一步探讨了细菌对喹诺酮类药物的抗性机制,包括染色体编码药物靶酶DNA促旋酶(DNA gyrase)和拓扑异构酶Ⅳ(topoisomerase Ⅳ)的点突变,染色体编码的调节蛋白突变所引发的药物输入蛋白下调或药物输出蛋白上调,以及质粒编码的可阻断药物与靶酶的相互作用、增加药物输出和改变药物代谢等抗性蛋白。研究喹诺酮的抗菌原理及细菌对喹诺酮的抗性机制,将有助于筛查和防控喹诺酮耐药菌。

Abstract:

Quinolones are one of the most commonly classes of antibacterials in the world,and the rise in resistance resulting from the wide use and/or the overuse threatens the clinical utility of this important drug class. This review describes the development of the quinolones,the mechanistic basis for quinolones targeting bacterial gyrase and topoisomerase Ⅳ to inhibit DNA replication. It further discusses the following mechanisms of bacterial resistance against quinolones. The most common and clinically significant resistance form is caused by mutations in chromosome-encoded enzymes DNA gyrase and topoisomerase Ⅳ. The mutations in chromosome-encoded regulators results in the underexpression of influx porins or the overexpression of efflux pumps. Plasmid-mediated resistance results from the proteins that disrupt quinolone-enzyme interactions, increase quinolone efflux, or alter drug metabolism. Thoroughly understanding of quinolone action and resistance mechanisms will significantly help to monitor, prevent and control drug-resistant bacteria in clinic.