Wang Nan, Meng Fanrong, Deng Li, Wu Ling, Yang Yu, Li Hua, Chen Yuanjin, Wei Zeyou, Xie Bei, Gong Lan, Niu Qun, Lei Jie, Gao Junwen, Huang Bo, Wang Qi, Lai Xiaomin, Liu Zhihui, Hu Jinxing
State Key Laboratory of Respiratory Disease, Guangzhou Key Laboratory of Tuberculosis Research, Institute of Pulmonary Diseases, Guangzhou Chest Hospital, Institute of Tuberculosis, Guangzhou Medical University, Guangdong, People's Republic of China.
Guangzhou Medical University.
Emerg Microbes Infect. 2025 Dec;14(1):2447607. doi: 10.1080/22221751.2024.2447607. Epub 2025 Jan 8.
This study investigates the epidemic trend of pyrazinamide (PZA)-resistant tuberculosis in Southern China over 11 years (2012-2022) and evaluates the mutation characteristics of PZA resistance-related genes ( and ) in clinical () isolates. To fulfil these goals, we analyzed the phenotypic PZA resistance characteristics of 14,927 clinical isolates for which Bactec MGIT 960 PZA drug susceptibility testing (DST) results were available, revealing that 2,054 (13.76%) isolates were resistant to PZA. After evaluating the annual variation in the PZA resistance rate among tuberculosis cases in this region, it was observed that it decreased from 37.21% to 6.45% throughout the initial 7 years (2012-2018) and then increased from 8.01% to 12.12% over the subsequent 4 years (2019-2022). Sequences of were obtained from 402 clinical complex isolates. For and sequences were obtained from 360 clinical complex isolates. Mutations in were found in 8 out of 223 PZA-sensitive isolates (3.59%) and 105 of 179 (58.66%) PZA-resistant isolates. Conversely, non-synonymous mutations in were identified in 5 of 137 (3.65%) PZA-resistant isolates, whereas the mutation ratio of among PZA-sensitive isolates was high at 14.03% (31/221). This difference in the mutation rate was statistically significant (, chi-square test). No mutations were observed in the 137 PZA-resistant isolates, whereas two PZA-sensitive isolates harboured point mutations in , including one nonsense mutation (C433 T) and another C-69 T mutation. These findings indicate that and may not significantly contribute to the development of PZA resistance in clinical isolates.
本研究调查了中国南方11年（2012 - 2022年）期间耐吡嗪酰胺（PZA）结核病的流行趋势，并评估了临床分离株中PZA耐药相关基因（和）的突变特征。为实现这些目标，我们分析了14927株临床分离株的PZA表型耐药特征，这些分离株有Bactec MGIT 960 PZA药物敏感性试验（DST）结果，显示2054株（13.76%）分离株对PZA耐药。评估该地区结核病病例中PZA耐药率的年度变化后，观察到在最初7年（2012 - 2018年）期间从37.21%降至6.45%，随后4年（2019 - 2022年）从8.01%升至12.12%。从402株临床复合分离株中获得了序列。对于和，从360株临床复合分离株中获得了序列。在223株PZA敏感分离株中有8株（3.59%）发现了中的突变，在179株PZA耐药分离株中有105株（58.66%）发现了突变。相反，在137株（3.65%）PZA耐药分离株中有5株鉴定出中的非同义突变，而PZA敏感分离株中的突变率较高，为14.03%（31/221）。这种突变率的差异具有统计学意义（，卡方检验）。在137株PZA耐药分离株中未观察到突变，而两株PZA敏感分离株在中有点突变，包括一个无义突变（C433 T）和另一个C - 69 T突变。这些发现表明和可能对临床分离株中PZA耐药性的产生没有显著贡献。
