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Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China

Pyrazinamide (PZA) is widely used to treat drug-sensitive or multidrug resistance tuberculosis. However, conventional PZA susceptibility tests of clinical isolates are rather difficult because of the requirement of acid pH. Since resistance to pyrazinamide is primary mediated by mutation of pncA, an...

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Autores principales: Li, Kun, Yang, Zhongping, Gu, Jing, Luo, Ming, Deng, Jiaoyu, Chen, Yaokai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832174/
https://www.ncbi.nlm.nih.gov/pubmed/33505367
http://dx.doi.org/10.3389/fmicb.2020.594171
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author Li, Kun
Yang, Zhongping
Gu, Jing
Luo, Ming
Deng, Jiaoyu
Chen, Yaokai
author_facet Li, Kun
Yang, Zhongping
Gu, Jing
Luo, Ming
Deng, Jiaoyu
Chen, Yaokai
author_sort Li, Kun
collection PubMed
description Pyrazinamide (PZA) is widely used to treat drug-sensitive or multidrug resistance tuberculosis. However, conventional PZA susceptibility tests of clinical isolates are rather difficult because of the requirement of acid pH. Since resistance to pyrazinamide is primary mediated by mutation of pncA, an alternative way of PZA susceptibility test is to analyze the pyrazinamidase activities of Mycobacterium tuberculosis clinical isolates. Therefore, a database containing the full spectrum of pncA mutations along with pyrazinamidase activities will be beneficial. To characterize mutations of pncA in M. tuberculosis from Chongqing, China, the pncA gene was sequenced and analyzed in 465 clinical isolates. A total of 124 types of mutations were identified in 424 drug-resistant isolates, while no mutation was identified in the 31 pan-susceptible isolates. Ninety-four of the 124 mutations had previously been reported, and 30 new mutations were identified. Based on reported literatures, 294 isolates could be predicted resistant to pyrazinamide. Furthermore, pyrazinamidase activities of the 30 new mutations were tested using the Escherichia coli pncA gene knockout strain. The results showed that 24 of these new mutations (28 isolates) led to loss of pyrazinamidase activity and six (8 isolates) of them did not. Taken together, 322 isolates with pncA mutations could be predicted to be PZA resistant among the 424 drug-resistant isolates tested. Analysis of pncA mutations and their effects on pyrazinamidase activity will not only enrich our knowledge of comprehensive pncA mutations related with PZA resistance but also facilitate rapid molecular diagnosis of pyrazinamide resistance in M. tuberculosis.
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spelling pubmed-78321742021-01-26 Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China Li, Kun Yang, Zhongping Gu, Jing Luo, Ming Deng, Jiaoyu Chen, Yaokai Front Microbiol Microbiology Pyrazinamide (PZA) is widely used to treat drug-sensitive or multidrug resistance tuberculosis. However, conventional PZA susceptibility tests of clinical isolates are rather difficult because of the requirement of acid pH. Since resistance to pyrazinamide is primary mediated by mutation of pncA, an alternative way of PZA susceptibility test is to analyze the pyrazinamidase activities of Mycobacterium tuberculosis clinical isolates. Therefore, a database containing the full spectrum of pncA mutations along with pyrazinamidase activities will be beneficial. To characterize mutations of pncA in M. tuberculosis from Chongqing, China, the pncA gene was sequenced and analyzed in 465 clinical isolates. A total of 124 types of mutations were identified in 424 drug-resistant isolates, while no mutation was identified in the 31 pan-susceptible isolates. Ninety-four of the 124 mutations had previously been reported, and 30 new mutations were identified. Based on reported literatures, 294 isolates could be predicted resistant to pyrazinamide. Furthermore, pyrazinamidase activities of the 30 new mutations were tested using the Escherichia coli pncA gene knockout strain. The results showed that 24 of these new mutations (28 isolates) led to loss of pyrazinamidase activity and six (8 isolates) of them did not. Taken together, 322 isolates with pncA mutations could be predicted to be PZA resistant among the 424 drug-resistant isolates tested. Analysis of pncA mutations and their effects on pyrazinamidase activity will not only enrich our knowledge of comprehensive pncA mutations related with PZA resistance but also facilitate rapid molecular diagnosis of pyrazinamide resistance in M. tuberculosis. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7832174/ /pubmed/33505367 http://dx.doi.org/10.3389/fmicb.2020.594171 Text en Copyright © 2021 Li, Yang, Gu, Luo, Deng and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Li, Kun
Yang, Zhongping
Gu, Jing
Luo, Ming
Deng, Jiaoyu
Chen, Yaokai
Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China
title Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China
title_full Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China
title_fullStr Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China
title_full_unstemmed Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China
title_short Characterization of pncA Mutations and Prediction of PZA Resistance in Mycobacterium tuberculosis Clinical Isolates From Chongqing, China
title_sort characterization of pnca mutations and prediction of pza resistance in mycobacterium tuberculosis clinical isolates from chongqing, china
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832174/
https://www.ncbi.nlm.nih.gov/pubmed/33505367
http://dx.doi.org/10.3389/fmicb.2020.594171
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