State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, China.
University of Chinese Academy of Sciences (UCAS), Beijing, China.
Microb Drug Resist. 2020 Jul;26(7):766-775. doi: 10.1089/mdr.2019.0245. Epub 2020 Jan 23.
Streptomycin (STR) is the first antibiotic used in the treatment of tuberculosis (TB) and the earliest antituberculosis drug with acquired resistance developed by The high prevalence of such resistance in many parts of the world limits its use for treating multidrug-resistant (MDR) TB. The aims of this study are to characterize of mutations in , , and genes in MDR isolates originating from southern China and to investigate possible relationship between mutations and strain genotypes for precise diagnosis and treatment. Sequences of , , and genes and the resistance profiles were analyzed for 218 MDR isolates. Our study showed that 68.35% of MDR isolates were resistant to STR and 89.91% of STR-resistant (STR) isolates were Beijing lineage strains. Mutations were observed in STR MDR isolates at the following rates: 72.48% in , 36.91% in , and 15.44% in . Compared with the phenotypic data, the combination of mutations in , , and has sensitivity and specificity of 96.64% and 100.00%, respectively. The most common mutations in STR isolates were 128,263 and 514,1401, of which 128 showed association with Beijing lineage ( < 0.001). It is noteworthy that a1401g mutation was present in , while MDR isolates were resistant to both STR and amikacin. Twenty two novel mutations were found in STR isolates. These findings could be helpful to develop rapid molecular diagnostic methods and understand STR resistance in China for developing TB precision medicine and disturbance of drug-resistant TB transmission.
链霉素（STR）是治疗肺结核（TB）的第一种抗生素，也是最早开发的具有获得性耐药性的抗结核药物。由于这种耐药性在世界许多地区的高流行率，限制了其用于治疗耐多药（MDR）TB。本研究的目的是对来自中国南方的 MDR 分离株中的 、 和 基因的突变进行特征描述，并研究突变与菌株基因型之间的可能关系，以进行精确诊断和治疗。对 218 株 MDR 分离株的 、 、 和 基因序列及耐药谱进行分析。研究结果表明，68.35%的 MDR 分离株对 STR 耐药，89.91%的 STR 耐药（STR）分离株为北京谱系菌株。在 STR MDR 分离株中观察到以下突变率： 72.48%在 ，36.91%在 ，15.44%在 。与表型数据相比， 、 、 和 突变的组合具有 96.64%和 100.00%的敏感性和特异性。STR 分离株中最常见的突变是 128、263 和 514、1401，其中 128 与北京谱系相关（ < 0.001）。值得注意的是，a1401g 突变存在于 中，而 MDR 分离株对 STR 和阿米卡星均耐药。在 STR 分离株中发现了 22 种新的突变。这些发现有助于开发快速分子诊断方法，了解中国 STR 耐药性，为开发结核病精准医学和干扰耐药结核病传播提供帮助。
