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

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Title: Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
Authors: Shrestha, Dipti Browse this author
Maharjan, Bhagwan Browse this author
Thapa, Jeewan Browse this author →KAKEN DB
Akapelwa, Mwangala Lonah Browse this author
Bwalya, Precious Browse this author
Chizimu, Joseph Yamweka Browse this author
Nakajima, Chie Browse this author →KAKEN DB
Suzuki, Yasuhiko Browse this author →KAKEN DB
Keywords: pyrazinamide
Mycobacterium tuberculosis
Issue Date: 8-Sep-2022
Publisher: MDPI
Journal Title: Current Issues in Molecular Biology
Volume: 44
Issue: 9
Start Page: 4132
End Page: 4141
Publisher DOI: 10.3390/cimb44090283
Abstract: 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.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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