Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance

Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance

Without the proper information on pyrazinamide (PZA) susceptibility of <i>Mycobacterium tuberculosis</i> (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 regardi...

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Bibliographic Details
Main Authors: Dipti Shrestha, Bhagwan Maharjan, Jeewan Thapa, Mwangala Lonah Akapelwa, Precious Bwalya, Joseph Yamweka Chizimu, Chie Nakajima, Yasuhiko Suzuki
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Current Issues in Molecular Biology
Subjects:
pyrazinamide
<i>pncA</i>
URR
mutation
<i>Mycobacterium tuberculosis</i>
Online Access:https://www.mdpi.com/1467-3045/44/9/283
Description
Summary:Without the proper information on pyrazinamide (PZA) susceptibility of <i>Mycobacterium tuberculosis</i> (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 <i>pncA</i> and its upstream regulatory region (URR). A total of 211 MTB isolates were included in this study. Sequence analysis of <i>pncA</i> and its URR was performed to assess PZA resistance. First-line drug susceptibility testing, spoligotyping, and sequence analysis of <i>rpoB</i>, <i>katG</i>, the <i>inhA</i> regulatory region, <i>gyrA</i>, <i>gyrB</i>, and <i>rrs</i> were performed to assess their association with pncA mutation. Sequencing results reveal that 125 (59.2%) isolates harbored alterations in <i>pncA</i> and its URR. A total of 57 different mutation types (46 reported and 11 novel) were scattered throughout the whole length of the <i>pncA</i> gene. Eighty-seven isolates (41.2%) harbored mutations in <i>pncA</i>, causing PZA resistance in MTB. There was a more significant association of <i>pncA</i> alterations in MDR/pre-extensively drug-resistant (Pre-XDR) TB than in mono-resistant/pan-susceptible TB (<i>p</i> < 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.
ISSN:1467-3037
1467-3045

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