细菌对喹诺酮类抗菌药的分子耐药机制

Molecular Mechanisms of Resistance to Quinolones in Bacteria

喹诺酮类是目前临床上应用较多的抗菌药。然而 ,喹诺酮类耐药菌时有出现。就细菌对喹诺酮类抗菌药主要耐药机制从分子水平作一综述。 ( 1 )一般认为 ,喹诺酮类抗菌药通过结合细菌Ⅱ类拓扑异构酶 ,干扰细菌复制 ,而发挥抑菌作用。Ⅱ类拓扑异构酶变异时 ,细菌可逃脱喹诺酮类的抑菌作用。高水平的耐药由DNA回旋酶和拓扑异构酶Ⅳ同时发生变异造成。 ( 2 )细菌细胞壁是抗菌药进入的屏障。细胞壁组分脂多糖和孔蛋白的改变 ,可减少喹诺酮类的通透。 ( 3)有些细菌可利用“外排泵”主动将喹诺酮类排出 ,降低喹诺酮类在菌体内的积累浓度。 ( 4 )细菌的其他一些代谢因素也可影响喹诺酮类的抑菌作用。

Quinolones are antibiotics widely used in clinics. However, resistance to quinolones in pathogenic bacteria occurs at times. This article reviews the main mechanisms that bacteria develop to counteract quinolones. (1) Generally, Quinolones disturb bacterial DNA replication by binding topoisomerase type Ⅱ. Therefore, mutants with variation of topoisomerase type Ⅱ can evade the inhibition of quinolones. High level quinolone resistance require mutations in both DNA gyrase gene and topoisomerase Ⅳ gene. (2) Bacterial cell wall is the barrier for the entry of antibiotics. Certain changes of outer membrane components, such as lipopolysaccharide and porins, can reduce the permeation of quinolones. (3) Some bacteria can pump quinolones out by themselves, so that concentration of quinolones within them would be lower. (4) Some metabolism factors may alter the sensitivity of bacteria to quinolones.