中国陕西流行结核分枝杆菌分离株的分子特征及对贝达喹啉的体外药敏性。
Molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis isolates circulating in Shaanxi, China.
机构信息
Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Clinical Laboratory, Shaanxi Provincial Institute for Tuberculosis Control and Prevention, Xi'an, Shaanxi 710048, China.
National Clinical Laboratory on Tuberculosis, BeijingKey Laboratory for Drug Resistant Tuberculosis Research, BeijingChest Hospital, Capital Medical University, BeijingTuberculosis and Thoracic Tumor Institute, Beijing, 102206, China.
出版信息
Int J Infect Dis. 2020 Oct;99:163-170. doi: 10.1016/j.ijid.2020.07.044. Epub 2020 Jul 29.
OBJECTIVE
The aim of this study was to investigate the molecular characteristics and in vitro susceptibility to bedaquiline of Mycobacterium tuberculosis (MTB) isolates from Shaanxi, China.
METHODS
The minimum inhibitory concentration (MIC) of bedaquiline was determined using the microplate alamarBlue assay for 518 MTB isolates from Shaanxi. Isolates with MIC values of bedaquiline ≥0.12 μg/mL were sequenced for the atpE, Rv0678, and pepQ genes. Drug susceptibility testing and spoligotyping were also conducted for all strains.
RESULTS
Ten (1.93%) bedaquiline-resistant strains were isolated from 518 tuberculosis patients. The resistance rate of bedaquiline was not correlated to sex, age, treatment history, region, or genotype. Five bedaquiline-resistant isolates and one bedaquiline-susceptible isolate were found to carry Rv0678 mutations; six mutation types were identified, including G5T, A263G, C185T, G19deletion, C265T, and T323C. No mutations within the atpE and pepQ genes were observed.
CONCLUSIONS
Bedaquiline showed strong in vitro antibacterial activity against MTB isolates, and the Rv0678 gene serves as the major mechanism contributing to bedaquiline resistance among MTB isolates from Shaanxi, China. Three novel mutation types (G19deletion, C265T, and T323C) of the Rv0678 gene were associated with resistance to bedaquiline. Furthermore, in addition to the current three resistance-associated genes (atpE, Rv0678, and pepQ), other mechanisms of resistance to bedaquiline may exist that need further study.
目的
本研究旨在探讨中国陕西分枝杆菌（MTB）分离株的分子特征及对贝达喹啉的体外敏感性。
方法
采用微量肉汤 alamarBlue 法测定贝达喹啉对陕西 518 株 MTB 分离株的最低抑菌浓度（MIC）。贝达喹啉 MIC 值≥0.12μg/mL 的分离株进行 atpE、Rv0678 和 pepQ 基因测序。对所有菌株进行药敏试验和 spoligotyping。
结果
从 518 例结核病患者中分离出 10 株（1.93%）贝达喹啉耐药株。贝达喹啉的耐药率与性别、年龄、治疗史、地区或基因型无关。发现 5 株贝达喹啉耐药株和 1 株贝达喹啉敏感株携带 Rv0678 突变；共鉴定出 6 种突变类型，包括 G5T、A263G、C185T、G19 缺失、C265T 和 T323C。未观察到 atpE 和 pepQ 基因内的突变。
结论
贝达喹啉对 MTB 分离株具有较强的体外抗菌活性，Rv0678 基因是中国陕西 MTB 分离株对贝达喹啉耐药的主要机制。与贝达喹啉耐药相关的 3 种新的 Rv0678 基因突变类型（G19 缺失、C265T 和 T323C）。此外，除了目前的 3 种耐药相关基因（atpE、Rv0678 和 pepQ）外，可能还存在其他耐药机制，需要进一步研究。
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