Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam.
Identifieur interne : 000333 ( PubMed/Checkpoint ); précédent : 000332; suivant : 000334Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam.
Auteurs : Nguyen Thi Le Hang [Viêt Nam] ; Minako Hijikata [Japon] ; Shinji Maeda [Japon] ; Pham Huu Thuong [Viêt Nam] ; Jun Ohashi [Japon] ; Hoang Van Huan [Viêt Nam] ; Nguyen Phuong Hoang [Viêt Nam] ; Akiko Miyabayashi [Japon] ; Vu Cao Cuong [Viêt Nam] ; Shintaro Seto [Japon] ; Nguyen Van Hung [Viêt Nam] ; Naoto Keicho [Japon]Source :
- Scientific reports [ 2045-2322 ] ; 2019.
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.
DOI: 10.1038/s41598-019-51812-7
PubMed: 31653940
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and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Van Hung, Nguyen" sort="Van Hung, Nguyen" uniqKey="Van Hung N" first="Nguyen" last="Van Hung">Nguyen Van Hung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, National Lung Hospital, Hanoi, Vietnam.</nlm:affiliation><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Department of Microbiology, National Lung Hospital, Hanoi</wicri:regionArea><wicri:noRegion>Hanoi</wicri:noRegion></affiliation></author><author><name sortKey="Keicho, Naoto" sort="Keicho, Naoto" uniqKey="Keicho N" first="Naoto" last="Keicho">Naoto Keicho</name><affiliation wicri:level="3"><nlm:affiliation>The Research Institute of Tuberculosis JATA, Tokyo, Japan. nkeicho-tky@umin.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Research Institute of Tuberculosis JATA, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31653940</idno><idno type="pmid">31653940</idno><idno type="doi">10.1038/s41598-019-51812-7</idno><idno type="wicri:Area/PubMed/Corpus">000384</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000384</idno><idno type="wicri:Area/PubMed/Curation">000384</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000384</idno><idno type="wicri:Area/PubMed/Checkpoint">000333</idno><idno 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Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Maeda, Shinji" sort="Maeda, Shinji" uniqKey="Maeda S" first="Shinji" last="Maeda">Shinji Maeda</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Hokkaido, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Hokkaido</wicri:regionArea><wicri:noRegion>Hokkaido</wicri:noRegion></affiliation></author><author><name sortKey="Thuong, Pham Huu" sort="Thuong, Pham Huu" uniqKey="Thuong P" first="Pham Huu" last="Thuong">Pham Huu Thuong</name><affiliation wicri:level="1"><nlm:affiliation>Hanoi Lung Hospital, Hanoi, Vietnam.</nlm:affiliation><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Hanoi Lung Hospital, Hanoi</wicri:regionArea><wicri:noRegion>Hanoi</wicri:noRegion></affiliation></author><author><name sortKey="Ohashi, Jun" sort="Ohashi, Jun" uniqKey="Ohashi J" first="Jun" last="Ohashi">Jun Ohashi</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Van Huan, Hoang" sort="Van Huan, Hoang" uniqKey="Van Huan H" first="Hoang" last="Van Huan">Hoang Van Huan</name><affiliation wicri:level="1"><nlm:affiliation>Hanoi Lung Hospital, Hanoi, Vietnam.</nlm:affiliation><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Hanoi Lung Hospital, Hanoi</wicri:regionArea><wicri:noRegion>Hanoi</wicri:noRegion></affiliation></author><author><name sortKey="Hoang, Nguyen Phuong" sort="Hoang, Nguyen Phuong" uniqKey="Hoang N" first="Nguyen Phuong" last="Hoang">Nguyen Phuong Hoang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Hanoi Lung Hospital, Hanoi, Vietnam.</nlm:affiliation><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Department of Microbiology, Hanoi Lung Hospital, Hanoi</wicri:regionArea><wicri:noRegion>Hanoi</wicri:noRegion></affiliation></author><author><name sortKey="Miyabayashi, Akiko" sort="Miyabayashi, Akiko" uniqKey="Miyabayashi A" first="Akiko" last="Miyabayashi">Akiko Miyabayashi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Cuong, Vu Cao" sort="Cuong, Vu Cao" uniqKey="Cuong V" first="Vu Cao" last="Cuong">Vu Cao Cuong</name><affiliation wicri:level="1"><nlm:affiliation>Hanoi Department of Health, Hanoi, Vietnam.</nlm:affiliation><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Hanoi Department of Health, Hanoi</wicri:regionArea><wicri:noRegion>Hanoi</wicri:noRegion></affiliation></author><author><name sortKey="Seto, Shintaro" sort="Seto, Shintaro" uniqKey="Seto S" first="Shintaro" last="Seto">Shintaro Seto</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Van Hung, Nguyen" sort="Van Hung, Nguyen" uniqKey="Van Hung N" first="Nguyen" last="Van Hung">Nguyen Van Hung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, National Lung Hospital, Hanoi, Vietnam.</nlm:affiliation><country xml:lang="fr">Viêt Nam</country><wicri:regionArea>Department of Microbiology, National Lung Hospital, Hanoi</wicri:regionArea><wicri:noRegion>Hanoi</wicri:noRegion></affiliation></author><author><name sortKey="Keicho, Naoto" sort="Keicho, Naoto" uniqKey="Keicho N" first="Naoto" last="Keicho">Naoto Keicho</name><affiliation wicri:level="3"><nlm:affiliation>The Research Institute of Tuberculosis JATA, Tokyo, Japan. nkeicho-tky@umin.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Research Institute of Tuberculosis JATA, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31653940</PMID><DateRevised><Year>2020</Year><Month>01</Month><Day>08</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>1</Issue><PubDate><Year>2019</Year><Month>Oct</Month><Day>25</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Whole genome sequencing, analyses of drug resistance-conferring mutations, and correlation with transmission of Mycobacterium tuberculosis carrying katG-S315T in Hanoi, Vietnam.</ArticleTitle><Pagination><MedlinePgn>15354</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41598-019-51812-7</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hang</LastName><ForeName>Nguyen Thi Le</ForeName><Initials>NTL</Initials><AffiliationInfo><Affiliation>NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hijikata</LastName><ForeName>Minako</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maeda</LastName><ForeName>Shinji</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Hokkaido, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thuong</LastName><ForeName>Pham Huu</ForeName><Initials>PH</Initials><AffiliationInfo><Affiliation>Hanoi Lung Hospital, Hanoi, Vietnam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ohashi</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van Huan</LastName><ForeName>Hoang</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Hanoi Lung Hospital, Hanoi, Vietnam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoang</LastName><ForeName>Nguyen Phuong</ForeName><Initials>NP</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Hanoi Lung Hospital, Hanoi, Vietnam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miyabayashi</LastName><ForeName>Akiko</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cuong</LastName><ForeName>Vu Cao</ForeName><Initials>VC</Initials><AffiliationInfo><Affiliation>Hanoi Department of Health, Hanoi, Vietnam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seto</LastName><ForeName>Shintaro</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, JATA, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van Hung</LastName><ForeName>Nguyen</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Microbiology, National Lung Hospital, Hanoi, Vietnam.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Keicho</LastName><ForeName>Naoto</ForeName><Initials>N</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-8232-9448</Identifier><AffiliationInfo><Affiliation>The Research Institute of Tuberculosis JATA, Tokyo, Japan. nkeicho-tky@umin.ac.jp.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National Center for Global Health and Medicine, Tokyo, Japan. nkeicho-tky@umin.ac.jp.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate 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