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Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance

Without the proper information on pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis (MTB), PZA is inappropriately recommended for the treatment of both susceptible and multidrug-resistant tuberculosis (MDR-TB) in Nepal. This study aimed to collect information regarding PZA susceptibili...

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Autores principales: Shrestha, Dipti, Maharjan, Bhagwan, Thapa, Jeewan, Akapelwa, Mwangala Lonah, Bwalya, Precious, Chizimu, Joseph Yamweka, Nakajima, Chie, Suzuki, Yasuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497661/
https://www.ncbi.nlm.nih.gov/pubmed/36135195
http://dx.doi.org/10.3390/cimb44090283
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author Shrestha, Dipti
Maharjan, Bhagwan
Thapa, Jeewan
Akapelwa, Mwangala Lonah
Bwalya, Precious
Chizimu, Joseph Yamweka
Nakajima, Chie
Suzuki, Yasuhiko
author_facet Shrestha, Dipti
Maharjan, Bhagwan
Thapa, Jeewan
Akapelwa, Mwangala Lonah
Bwalya, Precious
Chizimu, Joseph Yamweka
Nakajima, Chie
Suzuki, Yasuhiko
author_sort Shrestha, Dipti
collection PubMed
description Without the proper information on pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis (MTB), PZA is inappropriately recommended for the treatment of both susceptible and multidrug-resistant tuberculosis (MDR-TB) in Nepal. This study aimed to collect information regarding PZA susceptibility in MTB isolates from Nepal by analyzing pncA and its upstream regulatory region (URR). A total of 211 MTB isolates were included in this study. Sequence analysis of pncA and its URR was performed to assess PZA resistance. First-line drug susceptibility testing, spoligotyping, and sequence analysis of rpoB, katG, the inhA regulatory region, gyrA, gyrB, and rrs were performed to assess their association with pncA mutation. Sequencing results reveal that 125 (59.2%) isolates harbored alterations in pncA and its URR. A total of 57 different mutation types (46 reported and 11 novel) were scattered throughout the whole length of the pncA gene. Eighty-seven isolates (41.2%) harbored mutations in pncA, causing PZA resistance in MTB. There was a more significant association of pncA alterations in MDR/pre-extensively drug-resistant (Pre-XDR) TB than in mono-resistant/pan-susceptible TB (p < 0.005). This first report on the increasing level of PZA resistance in DR-TB in Nepal highlights the importance of PZA susceptibility testing before DR-TB treatment.
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spelling pubmed-94976612022-09-23 Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance Shrestha, Dipti Maharjan, Bhagwan Thapa, Jeewan Akapelwa, Mwangala Lonah Bwalya, Precious Chizimu, Joseph Yamweka Nakajima, Chie Suzuki, Yasuhiko Curr Issues Mol Biol Article Without the proper information on pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis (MTB), PZA is inappropriately recommended for the treatment of both susceptible and multidrug-resistant tuberculosis (MDR-TB) in Nepal. This study aimed to collect information regarding PZA susceptibility in MTB isolates from Nepal by analyzing pncA and its upstream regulatory region (URR). A total of 211 MTB isolates were included in this study. Sequence analysis of pncA and its URR was performed to assess PZA resistance. First-line drug susceptibility testing, spoligotyping, and sequence analysis of rpoB, katG, the inhA regulatory region, gyrA, gyrB, and rrs were performed to assess their association with pncA mutation. Sequencing results reveal that 125 (59.2%) isolates harbored alterations in pncA and its URR. A total of 57 different mutation types (46 reported and 11 novel) were scattered throughout the whole length of the pncA gene. Eighty-seven isolates (41.2%) harbored mutations in pncA, causing PZA resistance in MTB. There was a more significant association of pncA alterations in MDR/pre-extensively drug-resistant (Pre-XDR) TB than in mono-resistant/pan-susceptible TB (p < 0.005). This first report on the increasing level of PZA resistance in DR-TB in Nepal highlights the importance of PZA susceptibility testing before DR-TB treatment. MDPI 2022-09-08 /pmc/articles/PMC9497661/ /pubmed/36135195 http://dx.doi.org/10.3390/cimb44090283 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shrestha, Dipti
Maharjan, Bhagwan
Thapa, Jeewan
Akapelwa, Mwangala Lonah
Bwalya, Precious
Chizimu, Joseph Yamweka
Nakajima, Chie
Suzuki, Yasuhiko
Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
title Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
title_full Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
title_fullStr Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
title_full_unstemmed Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
title_short Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
title_sort detection of mutations in pnca in mycobacterium tuberculosis clinical isolates from nepal in association with pyrazinamide resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497661/
https://www.ncbi.nlm.nih.gov/pubmed/36135195
http://dx.doi.org/10.3390/cimb44090283
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