中国氟喹诺酮耐药结核分枝杆菌gyr基因序列特征分析  

Molecular characteristics of gyr gene of fluoroquinolone⁃resistant mycobacterium tuberculosis in China

作　　者：孟繁荣[1] 杨瑜[1] 雷杰[1] 王楠[1] 李华 谢贝[1] 邓丽 牛群[1] 竺澎波[1] 高俊文[1] 刘志辉[1] MENG Fanrong;YANG Yu;LEI Jie;WANG Nan;LI Hua;XIE Bei;DENG Li;NIU Qun;ZHU Pengbo;GAO Junwen;LIU Zhihui(Key State Laboratory of respiratory diseases,Institute of Pulmonary Diseases,Guangzhou Chest Hospital,Guangzhou 510095,China)

机构地区：[1]广东省广州市胸科医院肺部疾病研究所,呼吸疾病国家重点实验室结核病实验室,广州510095

出　　处：《实用医学杂志》2020年第11期1503-1508,共6页The Journal of Practical Medicine

基　　金：“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项(编号:2018ZX10715004);广东省自然科学基金项目(编号:2018A030313550);广州市高水平临床重点专科和培育专科建设项目(编号:穗卫函[2019]155号)。

摘　　要：目的明晰我国氟喹诺酮类药物耐药结核分枝杆菌株gyrA、gyrB基因突变的分子特征。方法以检索式"quinolones resistance AND Mycobacterium tuberculosis AND(China OR Hong Kong OR Tai Wan OR Macon)"和"结核AND喹诺酮耐药"分别在英文数据库(pubmed、Embase、SciFinder)和中文数据库(万方、中国知网、中国生物医学文献服务系统与维普期刊资源服务平台)中检索有关我国结核分枝杆菌喹诺酮类药物耐药基因突变的研究文献,对符合纳入标准的文献中氟喹诺酮耐药基因gyrA、gyrB进行突变位点和氨基酸变化类型等计数资料的信息提取和分析。结果 32篇外文和23篇中文文献纳入研究,3 641株氟喹诺酮类耐药结核分枝杆菌的gyrA基因得到分析,其中1 958株同时分析了gyrB基因。3 641株耐药菌中,2 830株检测到gyrA基因突变(突变率为77.73%),共47种突变类型,均为氨基酸错义突变,其中单位点、双位点突变的发生率分别为75.83%和1.92%,94、90、91位密码子突变率分别为49.33%(1 796/3 641)、19.14%(697/3 641)、5.80%(211/3 641),出现频率最高的突变类型依次为Asp94Gly、Ala90Val、Asp94Ala、Asp94Asn、Ser91Pro、Asp94Try;1 958株耐药菌中,175株发生gyrB基因突变(突变率为8.94%),其中56株的29个突变类型为gyrB单基因突变,其余119株36种突变类型与gyrA基因突变共同发生,占gyrB序列突变的68%。结论我国结核分枝杆菌氟喹诺酮耐药株gyrA基因突变以94、90、91位密码子单位点突变为主;gyrB基因突变位点较为分散,常与gyrA基因突变伴随发生。Objective To investigate the characteristics of gyrA and gyrB gene mutation of fluoroquinolone(FQ)⁃resistant Mycobacterium tuberculosis(MTB)in China.Methods The articles related to the gene mutation of Quinolone resistance of MTB were searched in English databases(Pubmed,Embase and SciFinder)and Chinese databases(WANFANG MED ONLINE,China National Knowledge Internet,SinoMed and VIP database)with the retrieval formulas“Quinolones resistance and mycocobacterium tuberculosis and(China or hong kong or tai wan or macon)”and“tuberculosis and quinolone resistance”,respectively.The data of enrolled articles was analyzed following the screening and extracting information of mutation sites and types.Results A total of 32 English and 23 Chinese articles were included in this study.The gyrA gene of 3,641 FQ⁃resistant MTB isolates were analyzed,and among which,gyrB gene of 1,958 isolates were analyzed simultaneously.In the 3,641 FQ⁃resistant MTB isolates,a total of 47 mutation types of gyrA gene,which were amino acid missense mutations,had been detected.The rate of gyrA mutation was 77.73%(2830/3641),and the occurrence rates of unit point mutation and double site mutation were 75.83%and 1.92%,respectively.Among the gene mutation types,the rates of codons 94,90 and 91 were 49.33%(1796/3641),19.14%(697/3641)and 5.80%(211/3641),respectively.The highest mutation frequency was Asp94Gly,and followed by Ala90Val,Asp94Ala,Asp94Asn,Ser91Pro and Asp94Tyr.Among the 1958 FQ⁃resistant isolates,175 isolates had mutations in the gyrB gene(mutation rate was 8.94%),of which 29 mutation types of 56 isolates only occurred in gyrB gene,while 36 mutation types of 119 isolates occurred together with gyrA gene.Conclusion The single mutation at codons 94,90 and 91 is the main form of gyrA gene mutation in FQ⁃resistant MTB of China.Mutation of gyrB gene is rare and scattered and often occurring with gyrA gene mutation simultaneously.

关 键 词：结核分枝杆菌 氟喹诺酮耐药 GYRA GYRB 中国 

分 类 号：R446.5[医药卫生—诊断学]