Tan Yaoju, Su Biyi, Zheng Huiwen, Song Yuanyuan, Wang Yufeng, Pang Yu
Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangzhou, China.
National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Front Microbiol. 2017 Nov 30;8:2358. doi: 10.3389/fmicb.2017.02358. eCollection 2017.
Prothionamide (PTH) has been widely used in the treatment of tuberculosis (TB), especially multidrug resistant tuberculosis (MDR-TB), while data regarding prevalence of resistance-causing mutation is limited. In this study, we aimed to investigate the molecular characteristics of PTH-resistant MTB isolates, and also analyzed the risk factors for PTH resistance among (MTB) isolates in southern China. A total of 282 MTB isolates were enrolled in from Guangzhou Chest Hospital. Among these isolates, 46 (16.3%) were resistant to PTH. Statistical analysis revealed that PTH resistance was more likely to be associated with resistance to levofloxacin (LFX; OR: 2.18, 95% CI: 1.02-4.63; = 0.04). Of the 46 PTH-resistant MTB isolates, 37 (80.4%) isolates harbored 19 different mutation types, including 10 (21.7%) isolates with double nucleotide substitutions and 27 (58.7%) with single nucleotide substitution. The mutations in ethA (51.4%, 19/37) were most frequently observed among PTH-resistant isolates, followed by 16 (43.2%) in the promoter of inhA and 6 (16.2%) in inhA. In addition, no significant difference was found in the distribution of isolates with different mutation types between Beijing and non-Beijing genotypes ( > 0.05). In conclusion, our data demonstrate that high diversity of genetic mutations conferring PTH resistance is identified among MTB isolates from southern China. Mutations in inhA, ethA, mshA, and ndh genes confer increased resistance of MTB to PTH. Ancient Beijing genotype strains have higher proportion of drug resistance compared with modern Beijing strains. In addition, PTH resistance is more likely to be observed in the LFX-resistant MTB isolates.
丙硫异烟胺（PTH）已广泛用于治疗结核病（TB），尤其是耐多药结核病（MDR-TB），但关于导致耐药性突变的流行率数据有限。在本研究中，我们旨在调查耐PTH的结核分枝杆菌（MTB）分离株的分子特征，并分析中国南方MTB分离株中PTH耐药的危险因素。共有282株MTB分离株来自广州胸科医院。在这些分离株中，46株（16.3%）对PTH耐药。统计分析显示，PTH耐药更可能与左氧氟沙星（LFX）耐药相关（OR：2.18，95%CI：1.02-4.63；P = 0.04）。在46株耐PTH的MTB分离株中，37株（80.4%）分离株存在19种不同的突变类型，包括10株（21.7%）双核苷酸替换和27株（58.7%）单核苷酸替换。在耐PTH分离株中，ethA突变最常见（51.4%，19/37），其次是inhA启动子区16株（43.2%）和inhA基因6株（16.2%）。此外，北京基因型和非北京基因型分离株中不同突变类型的分布无显著差异（P>0.05）。总之，我们的数据表明，在中国南方的MTB分离株中发现了赋予PTH耐药性的基因突变具有高度多样性。inhA、ethA、mshA和ndh基因的突变使MTB对PTH的耐药性增加。古代北京基因型菌株的耐药比例高于现代北京菌株。此外，耐LFX的MTB分离株中更易观察到PTH耐药。
