Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Tongzhou District, Beijing101149, China.
Beijing Changping Center for Tuberculosis Control and Prevention, Changping District, Beijing102200, China.
Epidemiol Infect. 2021 Jan 5;149:e21. doi: 10.1017/S0950268820003131.
The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at -15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (-15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.
本研究旨在探讨与异烟肼（INH）和利福平（RIF）耐药相关的基因突变在中国北京耐多药结核分枝杆菌（MDR-TB）菌株中的频率和分布。在这项回顾性研究中，通过 spoligotyping 分析了 173 株 MDR-TB 菌株的基因型。对 katG、inhA 基因及其 inhA 启动子区域（赋予 INH 耐药的基因突变）和 rpoB 基因（赋予 RIF 耐药的基因突变）进行了测序。还分析了不同基因型菌株中耐药相关核苷酸改变的百分比。总共，90.8%（157/173）的 MDR 菌株属于北京基因型。不同基因型菌株的人群特征无显著差异。总共，50.3%（87/173）的菌株 katG 基因的 S315T 密码子发生突变；16.8%（29/173）的菌株 inhA 启动子区域发生突变；其中，5.5%（15/173）的菌株 inhA 启动子区域的-15 位碱基（C→T）发生点突变。总共，86.7%（150/173）的菌株 rpoB 基因发生突变；其中，40%（69/173）的菌株 rpoB 基因的 S531L 发生突变。北京基因型 MDR 菌株的突变频率并不明显高于非北京基因型。北京基因型 MDR-TB 菌株在北京传播，对该地区的结核病控制构成重大挑战。观察到 katG Ser315Thr、inhA 启动子区域（-15C→T）和 rpoB（S531L）突变的高发生率。基于基因突变的分子诊断是快速检测中国北京地区 MDR-TB 的一种有用方法。
