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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Main Authors: Kanwara Trisakul, Ditthawat Nonghanphithak, Pratchakan Chaiyachat, Orawee Kaewprasert, Kankanon Sakmongkoljit, Wipa Reechaipichitkul, Angkana Chaiprasert, David Blair, Taane G. Clark, Kiatichai Faksri
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Emerging Microbes and Infections
Subjects:
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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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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