广西边境地区与非边境地区结核分枝杆菌基因组学分析  

Genomic analysis of Mycobacterium tuberculosis in border and nonborder areas of Guangxi Zhuang Autonomous Region

作　　者：叶婧[1] 周崇兴[1] 林玫[1] 先晓敏 梁小烟 张影坤[1] 蓝如束 崔哲哲[1] YE Jing;ZHOU Chong-xing;LIN Mei;XIAN Xiao-min;LIANG Xiao-yan;ZHANG Ying-kun;LAN Ru-shu;CUI Zhe-zhe;无(Guangxi Zhuang Autonomous Region Centre for Disease Control and Prevention,Guangxi Key Laboratory for Major Infectious Disease Prevention and Control and Biosafety Emergency Response,Guangxi key discipline platform of tuberculosis control,Nanning 530028,Guangxi Zhuang Autonomous Region,China;School of Public Health,Guizhou Medical University;Jiangbin Hospital of Guangxi Zhuang Autonomous Region)

机构地区：[1]广西壮族自治区疾病预防控制中心,广西重大传染病防控与生物安全应急响应重点实验室,广西结核病防治重点学科平台,广西南宁530028 [2]贵州医科大学公共卫生学院 [3]广西壮族自治区江滨医院

出　　处：《热带病与寄生虫学》2023年第2期82-87,共6页Journal of Tropical Diseases and Parasitology

基　　金：国家自然科学基金项目(82260656);广西卫生健康委科研项目(Z-A20220360、Z-A20220357);2019年广西医疗卫生适宜技术开发与应用推广项目(S2019065)。

摘　　要：目的分析广西边境地区和非边境地区结核分枝杆菌(Mycobacterium tuberculosis,MTB)基因型和耐药相关基因的分布特征。方法收集2015—2017年广西五个地区的结核病定点医疗机构的患者痰液标本,对边境地区(边境组)和非边境地区(非边境组)的MTB分离培养株进行对比研究。采用二代全基因组高通量测序技术对菌株进行基因分型,鉴定MTB菌株谱系,收集MTB耐药基因的变化信息。结果研究共纳入646株菌株。边境组199株,其中Lineage 1有8株(占4.02%),Lineage 2有126株(占63.32%),Lineage 3有1株(占0.01%),Lineage4有64株(占32.16%);非边境组447株,其中Lineage1有4株(占0.89%),Lineage 2有299株(占66.89%),Lineage4有144株(占32.21%),Lineage 3未见。边境组与非边境组基因型构成差异有统计学意义(χ^(2)=9.754,P<0.05)。其中Lineage 1和Lineage 4.2基因型在边境组和非边境组的分布差异有统计学意义(χ^(2)=5.763、4.833,P均<0.05)。有196株MTB分离株发生了耐药相关基因突变,其中边境组突变率(40.70%,81/199)高于非边境组(25.73%,115/447)(χ^(2)=14.613,P<0.05)。突变率前5的耐药基因依次是kat G(15.94%,103/646)、rop B(11.30%,73/646)、emb B(6.04%,39/646)、rps L(5.88%,38/646)和rrs L(3.72%,24/646)。其中kat G、rop B、rps L基因在边境组的突变率均高于非边境组(χ^(2)=5.716、9.603、6.979,P均<0.05),对应的kat G315、rpo B450、rps L43基因位点在边境组与非边境组的分布差异也均具有统计学意义(χ^(2)=5.153、12.893、11.693,P均<0.05)。结论广西MTB菌株出现Lineage 1和Lineage 3谱系,可能从邻国传入,需要进一步研究。广西耐药相关基因位点突变的分布与MTB基因型构成有一定的相关性。Objective To analyze the distribution of genotype characteristics and drug resistance-related genes of Mycobacterium tuberculosis(MTB)in border and non-border areas of Guangxi.Methods Sputum samples were collected from tuberculosis patients in designated medical institutions in five regions of Guangxi from 2015 to 2017,and MTB isolates from border and non-border cities were compared.The next-generation whole genome with high-throughput sequencing technology was used to genotype the strains,identify the MTB lineage and collect information on changes in MTB resistance genes.Results A total of 646 strains were included in the study,including 199 strains in the border group.Among them,8 strains were found in Lineage 1(4.02%),126 strains in Lineage 2(63.32%),1 strain in Lineage 3(0.01%),and 64 strains in Lineage 4(32.16%).447 strains were identified in the non-border group,including 4 strains in Lineage 1(0.89%),299 strains in Lineage 2(66.89%),and 144 strains in Lineage 4(32.21%).Lineage 3 was absent in this group.There was significant difference in the distribution of genotype composition between border and non-border group(χ^(2)=9.754,P<0.05).The difference was significant in the distribution of Lineage 1 and Lineage 4.2 genotypes between border and non-border group(χ^(2)=5.763,4.833,all P<0.05).Mutations occurred in 196 MTB isolates with drug-resistance related gene,in which the mutation rate in border group was 40.70%(81/199),higher than 25.73%(115/447)in non-border group(χ^(2)=14.613,P<0.05).The top 5 drug resistance genes with mutation rate from high to low were katG(15.94%,103/646),ropB(11.30%,73/646),embB(6.04%,39/646),rpsL(5.88%,38/646)and rrsL(3.72%,24/646).The mutation rate of katG,ropB and rpsL genes was higher in border group than in non-border group(χ^(2)=5.716,9.603,6.979,all P<0.05).The distribution of corresponding katG315,rpoB450 and rpsL43 gene loci in border and non-border group was also significant different(χ^(2)=5.153,12.893,11.693,all P<0.05).Conclusion The emergence of Lineage 1 and Line

关 键 词：结核分枝杆菌 全基因组测序 基因分型 谱系 耐药基因突变 广西 

分 类 号：R52[医药卫生—内科学]