High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates
Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) make TB difficult to control. Global susceptibility data for six newly recommended anti-TB drugs against M/XDR-TB are still limited. Using publicly available whole-genome sequences, we determined the propo...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2022-12-01
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Series: | Emerging Microbes and Infections |
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Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2022.2099304 |
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author | Kanwara Trisakul Ditthawat Nonghanphithak Pratchakan Chaiyachat Orawee Kaewprasert Kankanon Sakmongkoljit Wipa Reechaipichitkul Angkana Chaiprasert David Blair Taane G. Clark Kiatichai Faksri |
author_facet | Kanwara Trisakul Ditthawat Nonghanphithak Pratchakan Chaiyachat Orawee Kaewprasert Kankanon Sakmongkoljit Wipa Reechaipichitkul Angkana Chaiprasert David Blair Taane G. Clark Kiatichai Faksri |
author_sort | Kanwara Trisakul |
collection | DOAJ |
description | Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) make TB difficult to control. Global susceptibility data for six newly recommended anti-TB drugs against M/XDR-TB are still limited. Using publicly available whole-genome sequences, we determined the proportion of 513 phenotypically XDR-TB isolates that carried mutations associated with resistance against these drugs (bedaquiline, clofazimine, linezolid, delamanid, pretomanid and cycloserine). Mutations of Rv0678 and Rv1979c were detected in 69/513 isolates (13.5%) for bedaquiline resistance and 79/513 isolates (15.4%) for clofazimine resistance with additional mmpL5 mutations. Mutations conferring resistance to delamanid were detected in fbiB and ddn genes for 11/513 isolates (2.1%). For pretomanid, a mutation was detected in the ddn gene for 3/513 isolates (0.6%). Nineteen mutations of pykA, cycA, ald, and alr genes, conferring resistance to cycloserine, were found in 153/513 isolates (29.8%). No known mutations associated with linezolid resistance were detected. Cluster analysis showed that 408/513 isolates fell within 99 clusters and that 354 of these isolates were possible primary drug-resistant TB (292 XDR-TB, 57 pre-XDR-TB and 5 MDR-TB). Clonal transmission of primary XDR isolates might contribute significantly to the high prevalence of DR-TB globally. |
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language | English |
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publishDate | 2022-12-01 |
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series | Emerging Microbes and Infections |
spelling | doaj.art-82789c6aa9c342c2b4e26d84e9cc18d52022-12-22T00:58:50ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512022-12-011111857186610.1080/22221751.2022.2099304High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolatesKanwara Trisakul0Ditthawat Nonghanphithak1Pratchakan Chaiyachat2Orawee Kaewprasert3Kankanon Sakmongkoljit4Wipa Reechaipichitkul5Angkana Chaiprasert6David Blair7Taane G. Clark8Kiatichai Faksri9Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Geotechnology, Faculty of Technology, Khon Kaen University, Khon Kaen, ThailandDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandOffice for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandJames Cook University, Townsville, AustraliaLondon School of Hygiene and Tropical Medicine, London, UKDepartment of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandMultidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) make TB difficult to control. Global susceptibility data for six newly recommended anti-TB drugs against M/XDR-TB are still limited. Using publicly available whole-genome sequences, we determined the proportion of 513 phenotypically XDR-TB isolates that carried mutations associated with resistance against these drugs (bedaquiline, clofazimine, linezolid, delamanid, pretomanid and cycloserine). Mutations of Rv0678 and Rv1979c were detected in 69/513 isolates (13.5%) for bedaquiline resistance and 79/513 isolates (15.4%) for clofazimine resistance with additional mmpL5 mutations. Mutations conferring resistance to delamanid were detected in fbiB and ddn genes for 11/513 isolates (2.1%). For pretomanid, a mutation was detected in the ddn gene for 3/513 isolates (0.6%). Nineteen mutations of pykA, cycA, ald, and alr genes, conferring resistance to cycloserine, were found in 153/513 isolates (29.8%). No known mutations associated with linezolid resistance were detected. Cluster analysis showed that 408/513 isolates fell within 99 clusters and that 354 of these isolates were possible primary drug-resistant TB (292 XDR-TB, 57 pre-XDR-TB and 5 MDR-TB). Clonal transmission of primary XDR isolates might contribute significantly to the high prevalence of DR-TB globally.https://www.tandfonline.com/doi/10.1080/22221751.2022.2099304XDR-TBbedaquilineclofaziminelinezoliddelamanidpretomanid |
spellingShingle | Kanwara Trisakul Ditthawat Nonghanphithak Pratchakan Chaiyachat Orawee Kaewprasert Kankanon Sakmongkoljit Wipa Reechaipichitkul Angkana Chaiprasert David Blair Taane G. Clark Kiatichai Faksri High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates Emerging Microbes and Infections XDR-TB bedaquiline clofazimine linezolid delamanid pretomanid |
title | High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates |
title_full | High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates |
title_fullStr | High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates |
title_full_unstemmed | High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates |
title_short | High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates |
title_sort | high clustering rate and genotypic drug susceptibility screening for the newly recommended anti tuberculosis drugs among global extensively drug resistant mycobacterium tuberculosis isolates |
topic | XDR-TB bedaquiline clofazimine linezolid delamanid pretomanid |
url | https://www.tandfonline.com/doi/10.1080/22221751.2022.2099304 |
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