High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates

Journal Publication ResearchOnline@JCU
Trisakul, Kanwara;Nonghanphithak, Ditthawat;Chaiyachat, Pratchakan;Kaewprasert, Orawee;Sakmongkoljit, Kankanon;Reechaipichitkul, Wipa;Chaiprasert, Angkana;Blair, David;Clark, Taane G.;Faksri, Kiatichai
Abstract

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.

Journal

Emerging Microbes & Infections

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Volume

11

ISBN/ISSN

2222-1751

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1

Pages Count

10

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Publisher

Nature Publishing Group

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DOI

10.1080/22221751.2022.2099304