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

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

Shrestha, Dipti; Maharjan, Bhagwan; Thapa, Jeewan et al.

Current Issues in Molecular Biology, 2022, 44(9), 4132-4141

Permalink : https://hdl.handle.net/2115/87035

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アクセス権	metadata only access
URI	https://hdl.handle.net/2115/87035
タイトル	Detection of Mutations in pncA in Mycobacterium tuberculosis Clinical Isolates from Nepal in Association with Pyrazinamide Resistance
著者	Shrestha, Dipti ; Maharjan, Bhagwan ; Thapa, Jeewan ; Akapelwa, Mwangala Lonah ; Bwalya, Precious ; Chizimu, Joseph Yamweka ; Nakajima, Chie ; Suzuki, Yasuhiko
著者名 Shrestha, Dipti
著者名 Maharjan, Bhagwan
e-Rad_Researcher 40837449 著者名 Thapa, Jeewan
著者名 Akapelwa, Mwangala Lonah
著者名 Bwalya, Precious
著者名 Chizimu, Joseph Yamweka
e-Rad_Researcher 60435964 著者名 Nakajima, Chie
e-Rad_Researcher 90206540 著者名 Suzuki, Yasuhiko
言語	英語
キーワード	pyrazinamide
	pncA
	URR
	mutation
	Mycobacterium tuberculosis
発行日	2022-09-08
出版者	MDPI
収録物名	Current Issues in Molecular Biology
巻(号)	44(9)
ページ	4132-4141
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	1467-3037
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3390/cimb44090283