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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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/9/283 |
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| author | Dipti Shrestha Bhagwan Maharjan Jeewan Thapa Mwangala Lonah Akapelwa Precious Bwalya Joseph Yamweka Chizimu Chie Nakajima Yasuhiko Suzuki |
| author_facet | Dipti Shrestha Bhagwan Maharjan Jeewan Thapa Mwangala Lonah Akapelwa Precious Bwalya Joseph Yamweka Chizimu Chie Nakajima Yasuhiko Suzuki |
| author_sort | Dipti Shrestha |
| collection | DOAJ |
| description | 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. |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T00:22:27Z |
| publishDate | 2022-09-01 |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-16b27802f7ac4fbb84a8b7ac98844da82023-11-23T15:39:18ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-09-014494132414110.3390/cimb44090283Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide ResistanceDipti Shrestha0Bhagwan Maharjan1Jeewan Thapa2Mwangala Lonah Akapelwa3Precious Bwalya4Joseph Yamweka Chizimu5Chie Nakajima6Yasuhiko Suzuki7Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo 001-0020, JapanGerman Nepal Tuberculosis Project c/o Nepal Anti-Tuberculosis Association, Kalimati, Kathmandu 44600, NepalDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo 001-0020, JapanDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo 001-0020, JapanDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo 001-0020, JapanDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo 001-0020, JapanDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo 001-0020, JapanDivision of Bioresources, Hokkaido University International Institute for Zoonosis Control, Kita 20, Nishi 10, Kita-ku, Sapporo 001-0020, JapanWithout 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.https://www.mdpi.com/1467-3045/44/9/283pyrazinamide<i>pncA</i>URRmutation<i>Mycobacterium tuberculosis</i> |
| spellingShingle | Dipti Shrestha Bhagwan Maharjan Jeewan Thapa Mwangala Lonah Akapelwa Precious Bwalya Joseph Yamweka Chizimu Chie Nakajima Yasuhiko Suzuki Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance Current Issues in Molecular Biology pyrazinamide <i>pncA</i> URR mutation <i>Mycobacterium tuberculosis</i> |
| title | Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance |
| title_full | Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance |
| title_fullStr | Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance |
| title_full_unstemmed | Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance |
| title_short | Detection of Mutations in <i>pncA</i> in <i>Mycobacterium tuberculosis</i> Clinical Isolates from Nepal in Association with Pyrazinamide Resistance |
| title_sort | detection of mutations in i pnca i in i mycobacterium tuberculosis i clinical isolates from nepal in association with pyrazinamide resistance |
| topic | pyrazinamide <i>pncA</i> URR mutation <i>Mycobacterium tuberculosis</i> |
| url | https://www.mdpi.com/1467-3045/44/9/283 |
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