The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China

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 (pncA, rpsA, and panD) in clinical Mycobacterium tuberculosis (M. tuberculosis) isolates. To...

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Main Authors: Nan Wang, Fanrong Meng, Li Deng, Ling Wu, Yu Yang, Hua Li, Yuanjin Chen, Zeyou Wei, Bei Xie, Lan Gong, Qun Niu, Jie Lei, Junwen Gao, Bo Huang, Qi Wang, Xiaomin Lai, Zhihui Liu, Jinxing Hu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2024.2447607
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author Nan Wang
Fanrong Meng
Li Deng
Ling Wu
Yu Yang
Hua Li
Yuanjin Chen
Zeyou Wei
Bei Xie
Lan Gong
Qun Niu
Jie Lei
Junwen Gao
Bo Huang
Qi Wang
Xiaomin Lai
Zhihui Liu
Jinxing Hu
author_facet Nan Wang
Fanrong Meng
Li Deng
Ling Wu
Yu Yang
Hua Li
Yuanjin Chen
Zeyou Wei
Bei Xie
Lan Gong
Qun Niu
Jie Lei
Junwen Gao
Bo Huang
Qi Wang
Xiaomin Lai
Zhihui Liu
Jinxing Hu
author_sort Nan Wang
collection DOAJ
description 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 (pncA, rpsA, and panD) in clinical Mycobacterium tuberculosis (M. tuberculosis) 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 pncA were obtained from 402 clinical M. tuberculosis complex isolates. For rpsA and panD, sequences were obtained from 360 clinical M. tuberculosis complex isolates. Mutations in pncA 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 rpsA were identified in 5 of 137 (3.65%) PZA-resistant isolates, whereas the mutation ratio of rpsA among PZA-sensitive isolates was high at 14.03% (31/221). This difference in the rpsA mutation rate was statistically significant (P = 0.001, chi-square test). No panD mutations were observed in the 137 PZA-resistant isolates, whereas two PZA-sensitive isolates harboured point mutations in panD, including one nonsense mutation (C433 T) and another C-69 T mutation. These findings indicate that rpsA and panD may not significantly contribute to the development of PZA resistance in clinical M. tuberculosis isolates.
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spelling doaj-art-01b4d945401645ac95dc84ea4c2542332025-01-08T19:11:43ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2024.2447607The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern ChinaNan Wang0Fanrong Meng1Li Deng2Ling Wu3Yu Yang4Hua Li5Yuanjin Chen6Zeyou Wei7Bei Xie8Lan Gong9Qun Niu10Jie Lei11Junwen Gao12Bo Huang13Qi Wang14Xiaomin Lai15Zhihui Liu16Jinxing Hu17State 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaGuangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaState 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 ChinaState 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 ChinaState 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 ChinaState Key Laboratory of Respiratory Disease, Guangzhou Key Laboratory of Tuberculosis Research, Department of Tuberculosis, Guangzhou Chest Hospital, Institute of Tuberculosis, Guangzhou Medical University, Guangdong, People’s Republic of ChinaThis 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 (pncA, rpsA, and panD) in clinical Mycobacterium tuberculosis (M. tuberculosis) 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 pncA were obtained from 402 clinical M. tuberculosis complex isolates. For rpsA and panD, sequences were obtained from 360 clinical M. tuberculosis complex isolates. Mutations in pncA 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 rpsA were identified in 5 of 137 (3.65%) PZA-resistant isolates, whereas the mutation ratio of rpsA among PZA-sensitive isolates was high at 14.03% (31/221). This difference in the rpsA mutation rate was statistically significant (P = 0.001, chi-square test). No panD mutations were observed in the 137 PZA-resistant isolates, whereas two PZA-sensitive isolates harboured point mutations in panD, including one nonsense mutation (C433 T) and another C-69 T mutation. These findings indicate that rpsA and panD may not significantly contribute to the development of PZA resistance in clinical M. tuberculosis isolates.https://www.tandfonline.com/doi/10.1080/22221751.2024.2447607TuberculosispyrazinamideresistancepncArpsApanD
spellingShingle Nan Wang
Fanrong Meng
Li Deng
Ling Wu
Yu Yang
Hua Li
Yuanjin Chen
Zeyou Wei
Bei Xie
Lan Gong
Qun Niu
Jie Lei
Junwen Gao
Bo Huang
Qi Wang
Xiaomin Lai
Zhihui Liu
Jinxing Hu
The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China
Emerging Microbes and Infections
Tuberculosis
pyrazinamide
resistance
pncA
rpsA
panD
title The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China
title_full The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China
title_fullStr The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China
title_full_unstemmed The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China
title_short The epidemiology and gene mutation characteristics of pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates in Southern China
title_sort epidemiology and gene mutation characteristics of pyrazinamide resistant mycobacterium tuberculosis clinical isolates in southern china
topic Tuberculosis
pyrazinamide
resistance
pncA
rpsA
panD
url https://www.tandfonline.com/doi/10.1080/22221751.2024.2447607
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