江西省耐多药结核分枝杆菌链霉素基因突变特征

Study on the mutation characteristics of streptomycin genes of Multidrug-Resistant Mycobacterium Tuber⁃culosis in Jiangxi Province

目的了解江西省耐多药结核分枝杆菌中链霉素耐药的分子特征,探究北京基因型结核与链霉素耐药基因(rpsL、rrs和gidB)突变及链霉素耐药表型之间的关系。方法收集南昌大学第一附属医院高新医院及江西省胸科医院2021年1-12月分离的非重复耐多药结核菌106例,检测其耐药表型、是否为北京基因型及与链霉素耐药基因rpsL、rrs和gidB突变的关系。χ^(2)检验rpsL、rrs和gidB基因突变与北京基因型及表型关系。结果106例耐多药结核菌中链霉素耐药76例,其中58例rpsL 43A>G突变,8例88A>G突变,5例rrs突变,3例gidB突变。任何rpsL、rrs和gidB基因突变与表型耐药的符合率为89.6%,特异度及敏感度分别为86.7%和90.8%。北京型结核菌分离率为88.7%,其耐药基因突变主要集中于rpsL和rrs,非北京型菌耐药突变则主要集中于gidB;北京型菌更容易发生基因突变(P=0.013),但表型耐药无差异。结论rpsL、rrs和gidB基因突变与表型耐药符合率较好,可采用分子生物学直接检测耐药基因预判菌株耐药性;结核菌型与链霉素耐药特征具有紧密联系。

Objective To understand the molecular characteristics of Streptomycin(SM)resistance in multidrug-resistant tuberculosis(MDR-TB)in Jiangxi Province,and to explore the relationship between SM resistant genes(rpsL,rrs and gidB)mutations and SM resistant phenotypes in Beijing genotype TB.Methods 106 non-replicated MDR-TB isolates were collected from Gaoxin Branch of The First Affiliated Hospital of Nanchang University and Jiangxi Provincial Chest Hospital from January to December 2021,and tested for drug-resistance phenotypes,whether they were Beijing genotype or not and the characteristics of rpsL,rrs and gidB gene mutations.Chi-square test was performed to determine whether rpsL,rrs and gidB mutations were related to genotypes and drug-resistance phenotypes.Results Among 106 cases of MDR-TB,76 cases were resistant to SM.A total of 58 cases had rpsL 43A>G mutation,8 cases had 88A>G mutation,5 cases had rrs mutation,and 3 cases had gidB mutation.Statistical analysis showed that the coincidence rate of gene mutation and phenotypic drug-resistance detection was 89.6%,and the specificity and sensitivity were 86.7%and 90.8%,respectively.The isolated rate of Beijing genotype TB was 88.7%,and the drug-resistant gene mutations were mainly concentrated in rpsL and rrs,while the drug-resistant mutations of non-Beijing genotype were mainly concentrated in gidB;in addition,Beijing genotype bacteria were more prone to gene mutations(P=0.013),but there was no difference in phenotypic drug-resistance.Conclusions Mutations in rpsL,rrs,and gidB genes have a good coincidence rate with phenotypic drug-resistance,and molecular biology can be used to detect directly drug-resistance genes to predict bacterial resistance;TB genotypes are strongly associated with streptomycin resistance characteristics.