耐喹诺酮类药物革兰阴性菌的适应性研究

Study on the adaptability of quinolone-resistant Gram-negative bacteria

随着广谱高效喹诺酮类药物的过度应用,革兰阴性菌对喹诺酮类药物的耐药率逐年上升,已严重威胁到人类健康。革兰阴性菌对喹诺酮类药物的抗性是通过耐药基因突变或者获得外源抗性基因实现的。耐药性的维持通常会对细菌造成一定的适应性代价,表现为细菌生长速率、毒性和传播的减弱,但耐药菌可通过补偿突变缓解适应性代价,甚至增强耐药菌适应性,严重阻遏临床疗效。而且耐药菌株的适应性增强,导致细菌即使在缺乏抗菌剂使用的条件下,其耐药率也增加,导致无法通过减少抗菌剂的使用减弱菌株耐药率。所以本文分别对革兰阴性菌的染色体和PMQR基因介导的耐喹诺酮药物的机制对其适应性变化的影响进行综述,并对耐药菌适应性的研究方法进行总结,以期为耐喹诺酮类药物革兰阴性菌的新型治疗方案、相关的肠道致病菌抑制剂的开发和未来与之相关的研究提供一定参考。

With the excessive use of broad-spectrum high-efficiency quinolones,the resistance rate of gramnegative bacteria to quinolones has been increasing year by year,which has seriously threatened human health.Resistance to quinolones in gram-negative bacteria is achieved through mutations in resistance genes or acquisition of exogenous resistance genes.The maintenance of drug resistance usually causes a certain adaptive cost to bacteria,manifested as weakening of bacterial growth rate,toxicity and transmission,but drug-resistant bacteria can alleviate the adaptive cost by compensating mutations,and even enhance the adaptability of drug-resistant bacteria,seriously dampening the clinical effect.Moreover,the adaptability of resistant strains is enhanced,resulting in an increase in the resistance rate of bacteria even in the absence of antimicrobial use,resulting in the inability to attenuate the resistance rate of strains by reducing the use of antimicrobials.Therefore,in this paper,the effects of chromosome of gram-negative bacteria and PMQR gene-mediated mechanism of quinolone-resistant drugs on their adaptive changes are reviewed,and the research methods of adaptability of drug-resistant bacteria are summarized in order to provide some reference for new treatment regimens of quinolone-resistant Gram-negative bacteria,the development of related enteropathogen inhibitors and future related research.