广西壮族自治区结核分枝杆菌耐药基因突变特征及其与基因型的相关性分析

doi:10.3969/j.issn.1000-6621.2021.06.013

摘要/Abstract

摘要：

目的了解结核分枝杆菌对5种一线抗结核药品耐药相关基因突变特征及其与基因型的相关性。方法对2017年广西壮族自治区耐药监测收集的721株结核分枝杆菌进行全基因组测序,分析耐药相关基因突变特征及其与基因型的相关性。结果 223株结核分枝杆菌发生了耐药基因突变,总突变率为30.93%(223/721)。突变率前5位的基因为:katG(16.09%,116/721)、rpoB(12.21%,88/721)、embB(8.46%,61/721)、rpsL(6.10%,44/721)、rrs(4.72%,34/721),均以单位点突变为主;突变率前5位的基因位点为:katG315(12.34%,89/721)、rpsL43(5.27%,38/721)、rpoB450(4.85%,35/721)、embB306(4.02%,29/721)、rpoB445(2.91%,21/721)。rpsL基因、rpsL43位点和rpoB445位点突变率在北京基因型中高于非北京基因型[10.51%(43/409)和0.32%(1/312),χ²=32.090,P=0.000;9.05%(37/409)和0.32%(1/312),χ²=26.992,P=0.000; 4.40%(18/409)和0.96%(3/312),χ²=7.404,P=0.007]。结论广西壮族自治区结核分枝杆菌对一线抗结核药品耐药相关基因突变以katG、rpoB、embB、rpsL、rrs基因突变为主,rpsL基因、rpsL43位点和rpoB445位点突变与北京基因型有相关性。

关键词: 分枝杆菌,结核, 抗药性, 突变, 基因型

Abstract:

Objective To investigate the characteristics of Mycobacterium tuberculosis(MTB) gene mutation which are related with drug resistance to five first-line anti-tuberculosis drugs and their correlations with genotypes. Methods Whole-genome sequencing were performed on 721 MTB strains collected from drug resistance surveillance in Guangxi Zhuang Autonomous Region in 2017. Analyze the characteristics of drug resistance-related gene mutations and their correlation with genotypes. Results The total drug resistance-related gene mutation rate was 30.93% (223/721). The top 5 genes of mutation were katG (16.09%,116/721), rpoB (12.21%,88/721), embB (8.46%,61/721), rpsL (6.10%,44/721) and rrs (4.72%,34/721). The top 5 mutation loci were katG315 (12.34%,89/721), rpsL43 (5.27%,38/721), rpoB450 (4.85%,35/721), embB306 (4.02%,29/721) and rpoB445 (2.91%,21/721). RpsL, rpsL43 and rpoB445 mutation rate were higher in Beijing genotype strains than in non-Beijing genotype strains (10.51% (43/409) vs. 0.32% (1/312),χ²=32.090,P=0.000; 9.05% (37/409) vs. 0.32% (1/312),χ²=26.992,P=0.000; 4.40% (18/409) vs. 0.96% (3/312), χ²=7.404,P=0.007). Conclusion KatG,rpoB,embB,rpsL,rrs were the main drug resistance-related gene mutations in Guangxi MTB strains. The mutations in rpsL, rpsL43 and rpoB445 were correlated with Beijing genotype.

Key words: Mycobacterium tuberculosis, Drug resistance, Mutation, Genotype

罗丹, 覃慧芳, 叶婧, 赵锦明, 秦翊翔, 蓝如束. 广西壮族自治区结核分枝杆菌耐药基因突变特征及其与基因型的相关性分析[J]. 中国防痨杂志, 2021, 43(6): 596-601. doi: 10.3969/j.issn.1000-6621.2021.06.013

LUO Dan, QIN Hui-fang, YE Jing, ZHAO Jin-ming, QIN Yi-xiang, LAN Ru-shu. Analysis on gene mutation characteristics of drug resistant Mycobacterium tuberculosis and its correlation with genotypes in Guangxi[J]. Chinese Journal of Antituberculosis, 2021, 43(6): 596-601. doi: 10.3969/j.issn.1000-6621.2021.06.013

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药品	单药突变		多药联合突变		合计 (株)
药品	菌株数	构成比(%)	菌株数	构成比(%)	合计 (株)
异烟肼	58	40.85	84	59.15	142
利福平	15	17.05	73	82.95	88
链霉素	33	44.00	42	56.00	75
吡嗪酰胺	9	33.33	18	66.67	27
乙胺丁醇	11	17.19	53	82.81	64

药品	耐药基因	突变菌株数	突变率(%)
异烟肼	ahpC	7	0.97
	fabG1	11	1.53
	katG	114	15.81
	kasA	4	0.55
	inhA+fabG1	3	0.42
	kasA+fabG1	1	0.14
	katG+fabG1	2	0.28
利福平	rpoB	88	12.21
乙胺丁醇	embA	2	0.28
	embB	31	4.30
	embC	1	0.14
	embB+embA	4	0.55
	embB+embB	8	1.11
	embC+embB	18	2.50
吡嗪酰胺	pnaD	1	0.14
	pncA	26	3.61
链霉素	rpsL	41	5.69
	rrs	31	4.30
	rpsL+rrs	3	0.42

耐药基因	北京基因型(409株)	非北京基因型(312株)	χ²值	P值
katG	65(15.89)	51(16.35)	0.270	0.870
rpoB	55(13.45)	33(10.58)	1.361	0.243
embB	29(7.09)	32(10.26)	2.291	0.130
rpsL	43(10.51)	1(0.32)	32.090	0.000
rrs	20(4.89)	14(4.49)	0.639	0.800

突变位点	北京基因型(409株)	非北京基因型(312株)	χ²值	P值
katG315	52(12.71)	37(11.86)	0.119	0.730
rpoB450	21(5.13)	14(4.49)	0.161	0.689
rpsL43	37(9.05)	1(0.32)	26.992	0.000
embB306	16(3.91)	13(4.17)	0.030	0.863
rpoB445	18(4.40)	3(0.96)	7.404	0.007