Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting

Handle URI:
http://hdl.handle.net/10754/337670
Title:
Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting
Authors:
Perdigão, João; Silva, Hugo; Machado, Diana; Macedo, Rita; Maltez, Fernando; Silva, Carla; Jordao, Luisa; Couto, Isabel; Mallard, Kim; Coll, Francesc; Hill-Cawthorne, Grant A. ( 0000-0002-3828-5473 ) ; McNerney, Ruth; Pain, Arnab ( 0000-0002-1755-2819 ) ; Clark, Taane G; Viveiros, Miguel; Portugal, Isabel
Abstract:
Background Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades. Results In the present study we have genotyped and sequenced the genomes of 56 Mycobacterium tuberculosis isolates recovered mostly from Lisbon. The genotyping data revealed three major clusters associated with MDR-TB, two of which are associated with XDR-TB. Whilst the genomic data contributed to elucidate the phylogenetic positioning of circulating MDR-TB strains, showing a high predominance of a single SNP cluster group 5. Furthermore, a genome-wide phylogeny analysis from these strains, together with 19 publicly available genomes of Mycobacterium tuberculosis clinical isolates, revealed two major clades responsible for M/XDR-TB in the region: Lisboa3 and Q1 (LAM). The data presented by this study yielded insights on microevolution and identification of novel compensatory mutations associated with rifampicin resistance in rpoB and rpoC. The screening for other structural variations revealed putative clade-defining variants. One deletion in PPE41, found among Lisboa3 isolates, is proposed to contribute to immune evasion and as a selective advantage. Insertion sequence (IS) mapping has also demonstrated the role of IS6110 as a major driver in mycobacterial evolution by affecting gene integrity and regulation. Conclusions Globally, this study contributes with novel genome-wide phylogenetic data and has led to the identification of new genomic variants that support the notion of a growing genomic diversity facing both setting and host adaptation.
KAUST Department:
Pathogen Genomics Laboratory
Citation:
Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting 2014, 15 (1):991 BMC Genomics
Publisher:
Springer Nature
Journal:
BMC Genomics
Issue Date:
18-Nov-2014
DOI:
10.1186/1471-2164-15-991
PubMed ID:
25407810
PubMed Central ID:
PMC4289236
Type:
Article
ISSN:
1471-2164
Sponsors:
This work was partially supported by Project Ref. SDH49: “Early Molecular Detection of M/XDRTB in the Great Lisbon Healthcare Region” from Fundação Calouste Gulbenkian (FCG, Portugal) and PTDC/SAU-EPI/122400/2010 from Fundação para a Ciência e Tecnologia (FCT). The sequencing was funded by the KAUST Research Fund. J. Perdigão, D. Machado and C. Silva were supported by FCT grants SFRH/BPD/95406/2013, SFRH/BD/65060/2009 and SFRH/BD/73579/2010, respectively. TGC is funded by the Medical Research Council (UK) and Wellcome Trust.
Additional Links:
http://www.biomedcentral.com/1471-2164/15/991
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Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorPerdigão, Joãoen
dc.contributor.authorSilva, Hugoen
dc.contributor.authorMachado, Dianaen
dc.contributor.authorMacedo, Ritaen
dc.contributor.authorMaltez, Fernandoen
dc.contributor.authorSilva, Carlaen
dc.contributor.authorJordao, Luisaen
dc.contributor.authorCouto, Isabelen
dc.contributor.authorMallard, Kimen
dc.contributor.authorColl, Francescen
dc.contributor.authorHill-Cawthorne, Grant A.en
dc.contributor.authorMcNerney, Ruthen
dc.contributor.authorPain, Arnaben
dc.contributor.authorClark, Taane Gen
dc.contributor.authorViveiros, Miguelen
dc.contributor.authorPortugal, Isabelen
dc.date.accessioned2014-12-28T06:50:25Z-
dc.date.available2014-12-28T06:50:25Z-
dc.date.issued2014-11-18en
dc.identifier.citationUnraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting 2014, 15 (1):991 BMC Genomicsen
dc.identifier.issn1471-2164en
dc.identifier.pmid25407810en
dc.identifier.doi10.1186/1471-2164-15-991en
dc.identifier.urihttp://hdl.handle.net/10754/337670en
dc.description.abstractBackground Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades. Results In the present study we have genotyped and sequenced the genomes of 56 Mycobacterium tuberculosis isolates recovered mostly from Lisbon. The genotyping data revealed three major clusters associated with MDR-TB, two of which are associated with XDR-TB. Whilst the genomic data contributed to elucidate the phylogenetic positioning of circulating MDR-TB strains, showing a high predominance of a single SNP cluster group 5. Furthermore, a genome-wide phylogeny analysis from these strains, together with 19 publicly available genomes of Mycobacterium tuberculosis clinical isolates, revealed two major clades responsible for M/XDR-TB in the region: Lisboa3 and Q1 (LAM). The data presented by this study yielded insights on microevolution and identification of novel compensatory mutations associated with rifampicin resistance in rpoB and rpoC. The screening for other structural variations revealed putative clade-defining variants. One deletion in PPE41, found among Lisboa3 isolates, is proposed to contribute to immune evasion and as a selective advantage. Insertion sequence (IS) mapping has also demonstrated the role of IS6110 as a major driver in mycobacterial evolution by affecting gene integrity and regulation. Conclusions Globally, this study contributes with novel genome-wide phylogenetic data and has led to the identification of new genomic variants that support the notion of a growing genomic diversity facing both setting and host adaptation.en
dc.description.sponsorshipThis work was partially supported by Project Ref. SDH49: “Early Molecular Detection of M/XDRTB in the Great Lisbon Healthcare Region” from Fundação Calouste Gulbenkian (FCG, Portugal) and PTDC/SAU-EPI/122400/2010 from Fundação para a Ciência e Tecnologia (FCT). The sequencing was funded by the KAUST Research Fund. J. Perdigão, D. Machado and C. Silva were supported by FCT grants SFRH/BPD/95406/2013, SFRH/BD/65060/2009 and SFRH/BD/73579/2010, respectively. TGC is funded by the Medical Research Council (UK) and Wellcome Trust.en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.urlhttp://www.biomedcentral.com/1471-2164/15/991en
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectWhole genome sequencingen
dc.subjectMDR-TBen
dc.subjectXDR-TBen
dc.subjectLisboa familyen
dc.subjectMicroevolutionen
dc.titleUnraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant settingen
dc.typeArticleen
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.identifier.journalBMC Genomicsen
dc.identifier.pmcidPMC4289236en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCentro de Patogénese Molecular, URIA, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugalen
dc.contributor.institutionGrupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Lisboa, Portugalen
dc.contributor.institutionPublic Health Department, Public Health Laboratory: Mycobacteriology/Tuberculosis, Administração Regional de Saúde de Lisboa e Vale do Tejo, I.P, Lisboa, Portugalen
dc.contributor.institutionServiço de Infecciologia, Hospital de Curry Cabral, Lisboa, Portugalen
dc.contributor.institutionDepartamento de Doenças Infecciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugalen
dc.contributor.institutionCentro de Recursos Microbiológicos (CREM), Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Lisboa, Portugalen
dc.contributor.institutionFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UKen
dc.contributor.institutionSydney Emerging Infections and Biosecurity Institute and School of Public Health, Sydney Medical School, University of Sydney, Sydney NSW 2006, Australiaen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorHill-Cawthorne, Grant A.en
kaust.authorPain, Arnaben

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