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Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro

PURPOSE: Linezolid (LZD) and pretomanid (PA-824) are promising candidates in regimens for the treatment of drug-resistant tuberculosis. However, research on LZD and PA-824 dual drug-resistant (LPDR) strains is rarely reported. This study aimed to investigate the genotypic and virulence characteristi...

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Autores principales: Hu, Minghao, Fu, Lei, Wang, Bin, Xu, Jian, Guo, Shaochen, Zhao, Jiaojie, Li, Yuanyuan, Chen, Xiaoyou, Lu, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297343/
https://www.ncbi.nlm.nih.gov/pubmed/32606825
http://dx.doi.org/10.2147/IDR.S257145
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author Hu, Minghao
Fu, Lei
Wang, Bin
Xu, Jian
Guo, Shaochen
Zhao, Jiaojie
Li, Yuanyuan
Chen, Xiaoyou
Lu, Yu
author_facet Hu, Minghao
Fu, Lei
Wang, Bin
Xu, Jian
Guo, Shaochen
Zhao, Jiaojie
Li, Yuanyuan
Chen, Xiaoyou
Lu, Yu
author_sort Hu, Minghao
collection PubMed
description PURPOSE: Linezolid (LZD) and pretomanid (PA-824) are promising candidates in regimens for the treatment of drug-resistant tuberculosis. However, research on LZD and PA-824 dual drug-resistant (LPDR) strains is rarely reported. This study aimed to investigate the genotypic and virulence characteristics of LPDR strains. METHODS: To obtain the LPDR strains (marked as LP or PL strains), we used a two-way induction method, namely, we first induced LZD- or PA-824-resistant mutants from the parental Mycobacterium tuberculosis (MTB) strain H37Rv in vitro, then we obtained the LPDR strains from induction of LZD- or PA-824-resistant mutants. Mutations in rplC, rrl, or ddn and fgd1 were identified in all mutants. To investigate the virulence of these strains, six strains were selected as representative strains, including LZD-resistant strains, PA-824-resistant strains and LPDR strains. We performed the animal survival study as virulence of MTB can be measured as survival time of an animal after being infected. RESULTS: We induced 38 mutant strains of LZD and PA-824 mono or dual drug resistance from H37Rv in vitro. The mutation frequency of rplC (C154R) gene in LPDR strains was 100% and 86%, respectively. In the animal survival study, animals infected with different drug-resistant strains survived significantly longer than those infected with H37Rv; animals infected with LPDR strains and PA-824-resistant strains survived similarly and both of which survived significantly shorter than those infected with LZD-resistant strains. CONCLUSION: Our study showed that rplC gene had a high mutation frequency in LPDR strains. The virulence of LPDR strains was similar to PA-824-resistant strains, and the virulence of the LZD-resistant strains was weaker than PA-824-resistant strains.
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spelling pubmed-72973432020-06-29 Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro Hu, Minghao Fu, Lei Wang, Bin Xu, Jian Guo, Shaochen Zhao, Jiaojie Li, Yuanyuan Chen, Xiaoyou Lu, Yu Infect Drug Resist Original Research PURPOSE: Linezolid (LZD) and pretomanid (PA-824) are promising candidates in regimens for the treatment of drug-resistant tuberculosis. However, research on LZD and PA-824 dual drug-resistant (LPDR) strains is rarely reported. This study aimed to investigate the genotypic and virulence characteristics of LPDR strains. METHODS: To obtain the LPDR strains (marked as LP or PL strains), we used a two-way induction method, namely, we first induced LZD- or PA-824-resistant mutants from the parental Mycobacterium tuberculosis (MTB) strain H37Rv in vitro, then we obtained the LPDR strains from induction of LZD- or PA-824-resistant mutants. Mutations in rplC, rrl, or ddn and fgd1 were identified in all mutants. To investigate the virulence of these strains, six strains were selected as representative strains, including LZD-resistant strains, PA-824-resistant strains and LPDR strains. We performed the animal survival study as virulence of MTB can be measured as survival time of an animal after being infected. RESULTS: We induced 38 mutant strains of LZD and PA-824 mono or dual drug resistance from H37Rv in vitro. The mutation frequency of rplC (C154R) gene in LPDR strains was 100% and 86%, respectively. In the animal survival study, animals infected with different drug-resistant strains survived significantly longer than those infected with H37Rv; animals infected with LPDR strains and PA-824-resistant strains survived similarly and both of which survived significantly shorter than those infected with LZD-resistant strains. CONCLUSION: Our study showed that rplC gene had a high mutation frequency in LPDR strains. The virulence of LPDR strains was similar to PA-824-resistant strains, and the virulence of the LZD-resistant strains was weaker than PA-824-resistant strains. Dove 2020-06-12 /pmc/articles/PMC7297343/ /pubmed/32606825 http://dx.doi.org/10.2147/IDR.S257145 Text en © 2020 Hu et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Hu, Minghao
Fu, Lei
Wang, Bin
Xu, Jian
Guo, Shaochen
Zhao, Jiaojie
Li, Yuanyuan
Chen, Xiaoyou
Lu, Yu
Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro
title Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro
title_full Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro
title_fullStr Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro
title_full_unstemmed Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro
title_short Genetic and Virulence Characteristics of Linezolid and Pretomanid Dual Drug-Resistant Strains Induced from Mycobacterium tuberculosis in vitro
title_sort genetic and virulence characteristics of linezolid and pretomanid dual drug-resistant strains induced from mycobacterium tuberculosis in vitro
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297343/
https://www.ncbi.nlm.nih.gov/pubmed/32606825
http://dx.doi.org/10.2147/IDR.S257145
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