细菌黏菌素耐药性及其逆转机制研究进展  

Research Progress in Colistin (COL) Resistance in Bacterial and Its Reversal Mechanism

作　　者：胡功政[1] 崔小蝶 翟亚军 贺丹丹 HU Gong-zheng;CUI Xiao-die;ZHAI Ya-jun;HE Dan-dan(College of Veterinary Medicine,Henan Agricultural University,Zhengzhou 450046)

机构地区：[1]河南农业大学动物医学院,郑州450046

出　　处：《生物技术通报》2022年第9期28-34,共7页Biotechnology Bulletin

基　　金：国家自然科学基金面上项目(32072913);国家自然科学基金青年基金项目(32102716)。

摘　　要：黏菌素(colistin,COL)目前被认为是治疗多重耐药(multidrug-resistant,MDR)革兰氏阴性菌感染的最后一道防线。而随着COL使用的增长,世界范围内细菌COL耐药性也日益增长。研制具有新作用靶点的新抗菌药异常艰难,而逆转耐药性的联合用药是与MDR细菌斗争的经济有效策略。抗生素佐药针对细菌的非必须功能,并增强抗生素活性,可提供经济有效的方法逆转细菌耐药性。本文在概述COL作用机制、细菌耐药机制基础上,重点论述佐药对细菌COL耐药性的逆转作用及其逆转机制。目前已报道的COL耐药性逆转佐药有60余种,细菌被膜损害、外排泵机制、mcr-1基因的表达水平降低或MCR-1蛋白抑制被证明是重要的逆转机制。对COL耐药性逆转及逆转机制研究存在的问题进行了分析,并对其发展方向进行了展望。高效逆转佐药筛选、逆转作用的量效关系及其深入的机制研究,将是未来重要的发展方向。Colistin(COL)is presently considered the “last resort” of defense against human infections caused by multidrug-resistant Gram-negative bacteria.With the increasing use of COL,bacterial COL resistance is also increasing worldwide.It is extremely difficult to develop new antibacterial drugs with new targets,and combination drugs to reverse drug resistance are cost-effective strategies to combat MDR bacteria.Antibiotic adjuvants target non-essential functions of bacteria and enhance antibiotic activity,providing a cost-effective way to reverse bacterial resistance.Based on the summary of the action mechanism of COL and resistant mechanism in bacteria,this paper focuses on the reversal role of adjuvants on COL resistance in Gram-negative and its molecular mechanism are mainly discussed.More than 60 adjuvants that can reverse COL resistance have been reported to date.It has been proved that the disruption of the bacterial cell envelope,efflux pump inhibition are the expression decrease of mcr-1 gene or activity inhibition of MCR-1 protein the important mechanism of COL resistance reversal.The research status and existing problems on the reversal role of adjuvants on COL resistance and its molecular mechanism of adjuvants is analyzed,and its development trend is prospected.Screening of the efficient reversal adjuvants,dose-effect relationship of the reversal roles and in-depth mechanistic studies will be important development direction in the future.

关 键 词：黏菌素 耐药性逆转 逆转机制 作用机制 耐药机制 

分 类 号：S859.796[农业科学—临床兽医学]