华南地区380株结核分枝杆菌异烟肼耐药基因突变情况分析

doi:10.3760/cma.j.issn.1007-1245.2023.05.005

国际医药卫生导报 ›› 2023, Vol. 29 ›› Issue (5): 614-618.DOI: 10.3760/cma.j.issn.1007-1245.2023.05.005

华南地区380株结核分枝杆菌异烟肼耐药基因突变情况分析

邓丽王楠雷杰牛群吴玲龚兰谢贝王琪李华杨瑜刘志辉孟繁荣

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，广州　510095

收稿日期:2023-02-04 出版日期:2023-03-01 发布日期:2023-03-28
通讯作者: 孟繁荣，Email：rendong.mfr@163.com
基金资助:
广东省自然科学基金项目（2018A030313550、2023A1515010461）；广州市科技计划项目（202002030152）；广州市医学重点学科（2021-2023）结核病学；国家重点研发计划“病原学与防疫技术体系研究”重点专项（2022YFC2304800）

Analysis of isoniazid-resistant gene mutations in 380 strains of Mycobacterium tuberculosis in South China

Deng Li, Wang Nan, Lei Jie, Niu Qun, Wu Ling, Gong Lan, Xie Bei, Wang Qi, Li Hua, Yang Yu, Liu Zhihui, Meng Fanrong

Institute of Pulmonary Diseases, Guangzhou Chest Hospital, State Key Laboratory of Respiratory Diseases, Guangzhou 510095, China

Received:2023-02-04 Online:2023-03-01 Published:2023-03-28
Contact: Meng Fanrong, Email: rendong.mfr@163.com
Supported by:
Natural Science Foundation of Guangdong Province (2018A030313550, 2023A1515010461); Project of Science and Technology in Guangzhou (202002030152); Guangzhou Medical Key Discipline (2021-2023, Tuberculosis); "Etiology and Epidemic Prevention Technology System Research" Key Project of National Key Research and Development Program of China (2022YFC2304800)

摘要/Abstract

摘要：

目的　探讨华南地区异烟肼耐药结核分枝杆菌临床分离株katG、mabA-inhA、oxyR-ahpC、kasA和ndh基因的突变特点。方法　在广州地区分枝杆菌菌株库中，选择异烟肼耐药性测定结果明确的380株来自华南地区结核病患者的结核分枝杆菌临床分离株，其中异烟肼耐药株236株和异烟肼敏感株144株，对380株结核分枝杆菌临床分离株的5种异烟肼耐药基因片段进行序列测定分析。描述性分析各基因突变出现的频率。结果　在INH耐药株和敏感株中分别发现26个位点29种突变类型、16个位点17种突变类型，均以katG基因315AGC（S）→ACC（T）、mabA-inhA基因-15T→C最为常见，发生率分别为48.73%（115/236）、17.37%（41/236）和9.72%（14/144）、9.72%（14/144）；在katG、mabA-inhA、oxyR-ahpC、kasA和ndh中分别发现3个位点5种突变、5个位点5种突变、11个位点13种突变、6个位点6种突变和11个位点11种突变，在INH耐药株和敏感株中5个基因突变的发生率分别为52.12%（123/236）、22.46%（53/236）、5.93%（14/236）、1.69%（4/236）、2.54%（6/236）和11.11%（16/144）、11.11%（16/144）、4.17%（6/144）、1.39%（2/144）、3.47%（5/144）；在INH耐药株和敏感株中无基因突变、单基因突变、双基因以上突变发生率分别为27.12%（64/236）、61.44%（145/236）、11.44%（27/236）和76.39%（110/144）、21.53%（31/144）、2.08%（3/144）。结论　华南地区异烟肼耐药结核分枝杆菌临床分离株耐药基因突变具有其特点，敏感株中基因突变发生率较高，值得进一步深入研究。

关键词:

结核分枝杆菌, 药物敏感性, 异烟肼, 耐药基因

Abstract:

Objective　To explore the mutation characteristics of five genes (katG, mabA-inhA, oxyR-ahpC, kasA, and ndh) related to isoniazid resistance of Mycobacterium tuberculosis in clinical isolates in South China. Methods　A total of 380 clinical isolates of Mycobacterium tuberculosis from tuberculosis patients in South China which were sampled from the bio-bank of Mycobacteria in Guangzhou, including 236 isoniazid resistant strains and 144 isoniazid sensitive strains. The 5 isoniazid resistant gene fragments of 380 clinical isolates of Mycobacterium tuberculosis were sequenced and analyzed. Results　Twenty-nine gene mutation types at 26 sites in the isoniazid-resistant strains and 17 gene mutation types at 16 sites in the isoniazid-sensitive strains were found respectively. The most common mutations were 315AGC(S)→ACC(T) of katG and -15T→C of mabA-inhA, with the incidences of 48.73%(115/236), 17.37%(41/236), 9.72%(14/144), and 9.72%(14/144), respectively. Five mutations at 3 sites, 5 mutations at 5 sites, 13 mutations at 11 sites, 6 mutations at 6 sites, and 11 mutations at 11 sites were found in katG, mabA-inhA, oxyR-ahpC, kasA, and ndh, respectively. The incidences of five gene mutations in the isoniazid-resistant strains were 52.12%(123/236), 22.46%(53/236), 5.93%(14/236), 1.69%(4/236), and 2.54%(6/236) respectively, while those in the isoniazid-sensitive strains were 11.11%(16/144), 11.11%(16/144), 4.17%(6/144), 1.39%(2/144), and 3.47%(5/144), respectively. The incidences of no gene mutation, single gene mutation, and double gene mutations or more were 27.12% (64/236), 61.44% (145/236), and 11.44% (27/236) in the isoniazid-resistant strains and 76.39% (110/144), 21.53% (31/144), and 2.08% (3/144) in the isoniazid-sensitive strains. Conclusions　The gene mutation of isoniazid-resistant Mycobacterium tuberculosis in South China has its characteristics. It is essential to be studied further on the high gene mutation rate in isoniazid-sensitive strains.

Key words:

Mycobacterium tuberculosis, Drug susceptivity, Isoniazid, Drug resistant gene

邓丽王楠雷杰牛群吴玲龚兰谢贝王琪李华杨瑜刘志辉孟繁荣.

华南地区380株结核分枝杆菌异烟肼耐药基因突变情况分析 [J]. 国际医药卫生导报, 2023, 29(5): 614-618.

Deng Li, Wang Nan, Lei Jie, Niu Qun, Wu Ling, Gong Lan, Xie Bei, Wang Qi, Li Hua, Yang Yu, Liu Zhihui, Meng Fanrong.

Analysis of isoniazid-resistant gene mutations in 380 strains of Mycobacterium tuberculosis in South China [J]. International Medicine and Health Guidance News, 2023, 29(5): 614-618.

参考文献

[1] WHO. Global tuberculosis report 2021[R]. Geneva:WHO Press,2022. https://www.who.int/tb/publications/global_report/en/.
[2] 刘志辉,钟球.全面应对耐多药结核病的挑战——问题、困惑、行动和希望[J].实用医学杂志,2022,38(13):1573-1577. DOI:10.3969/j.issn.1006-5725.2022.13.001.
[3] 刘剑君,王黎霞.现代结核病学[M]. 2版. 北京:人民卫生出版社,2022:404-440.
[4] Dookie N, Ngema SL, Perumal R, et al. The changing paradigm of drug-resistant tuberculosis treatment: successes, pitfalls, and future perspectives[J]. Clin Microbiol Rev, 2022, 35(4): e0018019. DOI: 10.1128/cmr.00180-19.
[5] Kohli M, MacLean E, Pai M, et al. Diagnostic accuracy of centralised assays for TB detection and detection of resistance to rifampicin and isoniazid: a systematic review and meta-analysis[J]. Eur Respir J, 2021, 57(2): 2000747. DOI:10.1183/13993003.00747-2020.
[6] Bertram G Katzung. 基础与临床药理学[M]. 金有豫, 唐玉, 张殿增, 译. 13版. 北京: 人民卫生出版社, 2020: 679-687.
[7] Vilchèze C, Jacobs WR. The mechanism of isoniazid killing: clarity through the scope of genetics[J]. Annu Rev Microbiol, 2007, 61: 35-50. DOI: 10.1146/annurev.micro.61.111606.122346.
[8] CRyPTIC Consortium and the 100,000 Genomes Project, Allix-Béguec C, Arandjelovic I,et al. Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing[J]. N Engl J Med, 2018, 379(15): 1403-1415. DOI: 10.1056/NEJMoa1800474.
[9] Krittanan P, Srimanote P, Thawornwan U, et al. Spoligotype-based population structure and isoniazid-resistance gene mutation of Mycobacterium tuberculosis isolates from Thailand[J]. J Glob Antimicrob Resist, 2022, 30: 319-325. DOI: 10.1016/j.jgar.2022. 06.013.
[10] Narmandakh E, Tumenbayar O, Borolzoi T, et al. Genetic mutations associated with isoniazid resistance in mycobacterium tuberculosis in Mongolia[J]. Antimicrob Agents Chemother, 2020, 64(7): e00537-20. DOI: 10.1128/AAC.00537-20.
[11] Isakova J, Sovkhozova N, Vinnikov Denis, et al. Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic[J]. BMC Microbiol, 2018, 18(1): 22. DOI: 10.1186/s12866-018-1168-x.
[12] Huo F, Lu Jie, Zong Z, et al. Change in prevalence and molecular characteristics of isoniazid-resistant tuberculosis over a 10-year period in China[J]. BMC Infect Dis, 2019, 19(1): 689. DOI: 10.1186/s12879-019-4333-4.
[13] Ghodousi A, Tagliani E, Karunaratne E, et al. Isoniazid resistance in Mycobacterium tuberculosis is a heterogeneous phenotype composed of overlapping MIC distributions with different underlying resistance mechanisms[J]. Antimicrob Agents Chemother, 2019, 63(7): e00092-19. DOI: 10.1128/AAC.00092-19.

华南地区380株结核分枝杆菌异烟肼耐药基因突变情况分析

Analysis of isoniazid-resistant gene mutations in 380 strains of Mycobacterium tuberculosis in South China

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 0

编辑推荐

Metrics