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

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 pat...

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Autores principales:	Nguyen Thi Le Hang, Minako Hijikata, Shinji Maeda, Pham Huu Thuong, Jun Ohashi, Hoang Van Huan, Nguyen Phuong Hoang, Akiko Miyabayashi, Vu Cao Cuong, Shintaro Seto, Nguyen Van Hung, Naoto Keicho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50933eae54ce4905af9e6bf3947d763f
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spelling	oai:doaj.org-article:50933eae54ce4905af9e6bf3947d763f2021-12-02T16:08:05ZWhole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam10.1038/s41598-019-51812-72045-2322https://doaj.org/article/50933eae54ce4905af9e6bf3947d763f2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51812-7https://doaj.org/toc/2045-2322Abstract 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.Nguyen Thi Le HangMinako HijikataShinji MaedaPham Huu ThuongJun OhashiHoang Van HuanNguyen Phuong HoangAkiko MiyabayashiVu Cao CuongShintaro SetoNguyen Van HungNaoto KeichoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nguyen Thi Le Hang Minako Hijikata Shinji Maeda Pham Huu Thuong Jun Ohashi Hoang Van Huan Nguyen Phuong Hoang Akiko Miyabayashi Vu Cao Cuong Shintaro Seto Nguyen Van Hung Naoto Keicho Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam
description	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.
format	article
author	Nguyen Thi Le Hang Minako Hijikata Shinji Maeda Pham Huu Thuong Jun Ohashi Hoang Van Huan Nguyen Phuong Hoang Akiko Miyabayashi Vu Cao Cuong Shintaro Seto Nguyen Van Hung Naoto Keicho
author_facet	Nguyen Thi Le Hang Minako Hijikata Shinji Maeda Pham Huu Thuong Jun Ohashi Hoang Van Huan Nguyen Phuong Hoang Akiko Miyabayashi Vu Cao Cuong Shintaro Seto Nguyen Van Hung Naoto Keicho
author_sort	Nguyen Thi Le Hang
title	Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam
title_short	Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam
title_full	Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam
title_fullStr	Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam
title_full_unstemmed	Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam
title_sort	whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of mycobacterium tuberculosis carrying katg-s315t in hanoi, vietnam
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/50933eae54ce4905af9e6bf3947d763f
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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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