Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam.

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ID: 75489
2019
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Abstract
Drug-resistant tuberculosis (TB) is a serious global problem, and pathogen factors involved in the transmission of isoniazid (INH)-resistant TB have not been fully investigated. We performed whole genome sequencing of 332 clinical Mycobacterium tuberculosis (Mtb) isolates collected from patients newly diagnosed with smear-positive pulmonary TB in Hanoi, Vietnam. Using a bacterial genome-wide approach based on linear mixed models, we investigated the associations between 31-bp k-mers and clustered strains harboring katG-S315T, a major INH-resistance mutation in the present cohort and in the second panel previously published in South Africa. Five statistically significant genes, namely, PPE18/19, gid, emrB, Rv1588c, and pncA, were shared by the two panels. We further identified variants of the genes responsible for these k-mers, which are relevant to the spread of INH-resistant strains. Phylogenetic convergence test showed that variants relevant to PPE46/47-like chimeric genes were significantly associated with the same phenotype in Hanoi. The associations were further confirmed after adjustment for the confounders. These findings suggest that genomic variations of the pathogen facilitate the expansion of INH-resistance TB, at least in part, and our study provides a new insight into the mechanisms by which drug-resistant Mtb maintains fitness and spreads in Asia and Africa.
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hang2019wholescientific Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Hang, Nguyen Thi Le;Hijikata, Minako;Maeda, Shinji;Thuong, Pham Huu;Ohashi, Jun;Van Huan, Hoang;Hoang, Nguyen Phuong;Miyabayashi, Akiko;Cuong, Vu Cao;Seto, Shintaro;Van Hung, Nguyen;Keicho, Naoto;
Journal Scientific reports
Year 2019
DOI
10.1038/s41598-019-51812-7
URL
Keywords
immunity melanin cichlids oreochromis niloticus hemosiderin lipofuscin

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