氟喹诺酮耐药与结核分枝杆菌中gyrA和gyrB基因突变的研究进展  

Research Progress of the Association between Fluoroquinolone Resistance and Mutations in gyrA and gyrB Genes in Mycobacterium Tuberculosis

作　　者：王志锐[1] 谢彤[1] 

机构地区：[1]天津市疾病预防控制中心病原生物检测所,天津300011

出　　处：《医学综述》2017年第13期2516-2521,共6页Medical Recapitulate

基　　金：天津市疾病预防控制中心科技基金(CDCKY1503)

摘　　要：氟喹诺酮类药物虽然是二线抗结核药物之一,但它在治疗耐多药结核病过程中显得尤为重要。近年来,对氟喹诺酮类药物耐药的结核分枝杆菌不断增加。而结核分枝杆菌对氟喹诺酮类药物产生耐药性的分子机制主要是编码DNA解旋酶的gyr A和gyr B基因,其喹诺酮耐药决定区的突变与耐药性密切相关。目前,gyr A和gyr B基因中喹诺酮耐药决定区的突变类型有多种,但gyr B基因中与耐药表型相关联的突变位点较少,且常与gyr A基因中的突变共存。基于结核分枝杆菌gyr A和gyr B基因突变的分子诊断技术能快速检测氟喹诺酮耐药性,但仅限于常见的突变。而新型分子鉴定技术能检测所有有记录的结核分枝杆菌中与氟喹诺酮耐药相关的gyr A和gyr B基因突变。未来,对gyr A和gyr B基因突变的深入研究,将会改进和优化新型检测结核分枝杆菌氟喹诺酮耐药性的分子诊断技术。Fluoroquinolone, known as one of most effective second-line anti-microbial drugs, is important for the treat- ment of multidrug resistant tuberculosis. Recently, fluoroquinolone resistant Mycobacterium tuberculosis clinical isolates have been increasing worldwide. The main molecular mechanism of fluoroquinolone resistance in M. tuberculosis is the DNA gyrase coded by gyrA and gyrB genes,in which the mutations within quinolone resistance determining region are implicated to fluoroquinolone resistance. In the gyrA and gyrB genes, there are a number of the mutations within quinolone resistance determining region,however the mutations conferring fluoroquinolone resistance in gyrB are rare and often coexist with the mutations in gyrA. Molecular diagnosis based on mutations in the gyrA and gyrB can rapidly detect fluoroquinolone resis- tance, but is limited to the most common mutations in those genes. The next generation molecular assay will be able to detect all the documented gyrA and gyrB mutations associated with f/uoroquinolone resistance. In the future, further studies focusing on the gyrA and gyrB mutations will improve and optimize the next generation molecular diagnostic technology for detecting fluoroquinolone resistance in M. tuberculosis.

关 键 词：结核分枝杆菌 氟喹诺酮 耐药 DNA解旋酶 基因突变 

分 类 号：R378.911[医药卫生—病原生物学]