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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 |
| 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 | | pncA | | URR | | mutation | | 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 |
| URI: | http://hdl.handle.net/2115/87035 |
| 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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