江西省耐多药结核分枝杆菌链霉素基因突变特征

doi:10.3969/j.issn.1006-5725.2024.01.016

摘要/Abstract

摘要：

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。χ²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。

关键词: 耐多药结核菌, 链霉素耐药, 北京基因型, 江西省

Abstract:

Objective To understand the molecular characteristics of Streptomycin （SM） resistance in multidrug-resistanttuberculosis（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.

Key words: multidrug-resistant tuberculosis, streptomycin resistance, beijing genotype, Jiangxi province

中图分类号:

R378.91⁺1

于圣铭,夏良华,詹佳欢,刘思琦,王伟,晏亮,陈开森. 江西省耐多药结核分枝杆菌链霉素基因突变特征[J]. 实用医学杂志, 2024, 40(1): 91-96.

Shengming YU,Lianghua XIA,Jiahuan ZHAN,Siqi LIU,Wei WANG,Liang YAN,Kaisen. CHEN. Study on the mutation characteristics of streptomycin genes of Multidrug-Resistant Mycobacterium Tuberculosis in Jiangxi Province[J]. The Journal of Practical Medicine, 2024, 40(1): 91-96.

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突变类型	频率	百分比(%)
总计	106	100.0
未突变	33	31.1
单基因突变
rpsL突变
43A > G	58	54.7
88A > G	7	6.6
rrs突变
462C > T	1	0.9
514A > C	1	0.9
514A > T	2	1.9
517C > T	1	0.9
gidB突变
102delG	1	0.9
115delC	1	0.9
双基因突变
gid 102delG；rpsL 88A > G	1	0.9

谱系	基因突变情况		χ²值	P值	表型耐药情况		χ²值	P值
谱系	发生突变	未发生突变	χ²值	P值	R	S	χ²值	P值
北京基因型	69	25	6.210	0.013	69	25	0.564	0.453
非北京基因型	4	8	6.210	0.013	7	5	0.564	0.453

基因谱系	突变情况	频次	百分比（%）
北京基因型	未发生突变	25	26.6
	rpsL突变
	43A>G	56	59.6
	88A>G	7	7.4
	rrs突变
	462C>T	1	1.1
	514A>C	1	1.1
	514A>T	2	2.1
	517C>T	1	1.1
	gidB 102delG， rpsL 88A>G	1	1.1
	总计	94	100.0
非北京基因型	未发生突变	8	66.7
	rpsL 88A>G	2	16.7
	gidB突变
	102delG	1	8.3
	115delC	1	8.3
	总计	12	100.0

突变状况	表型结果	频次	百分比（%）
未发生突变	R	7	21.2
	S	26	78.8
总计		33	100.0
rpsL43A>G	R	57	98.3
	S	1	1.7
总计		58	100.0
rpsL88A>G	R	7	100.0
rrs突变
462C>T	S	1	100.0
514A>C	R	1	100.0
514A>T	S	2	100.0
517C>T	R	1	100.0
gidB突变
102delG	R	1	100.0
115delC	R	1	100.0
Gid102delG， rpsL 88A>G	R	1	100.0