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Using genomics to understand the origin and dispersion of multidrug and extensively drug resistant tuberculosis in Portugal

2020-02-13Journal article Open access
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dc.contributor.authorPerdigão, João
dc.contributor.authorGomes, Pedro
dc.contributor.authorMiranda, Anabela
dc.contributor.authorMaltez, Fernando
dc.contributor.authorMachado, Diana
dc.contributor.authorSilva, Carla
dc.contributor.authorPhelan, Jody E.
dc.contributor.authorBrum, Laura
dc.contributor.authorCampino, Susana
dc.contributor.authorCouto, Isabel
dc.contributor.authorViveiros, Miguel
dc.contributor.authorClark, Taane G.
dc.contributor.authorPortugal, Isabel
dc.date.accessioned2021-03-31T15:13:39Z
dc.date.available2021-03-31T15:13:39Z
dc.date.issued2020-02-13
dc.description.abstractPortugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR- and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach.pt_PT
dc.description.sponsorshipFinancial support was provided by the European Society of Clinical Microbiology and Infectious Diseases, for which we would like to would like to acknowledge the Study Group for Mycobacterial Infections. Supported in part by UID/DTP/04138/2019 from Fundação para a Ciência e Tecnologia (FCT), Portugal. JP [CEECIND/00394/2017] and DM are supported by FCT through Estímulo Individual ao Emprego Científico. DM, IC and MV are funded by project PTDC/BIA-MIC/30692/2017 and the Global Health and Tropical Medicine (GHTM) Research Center (Grant UID/Multi/04413/2013) from FCT. TGC received funding from the MRC UK (Grant no. MR/K000551/1, MR/M01360X/1, MR/N010469/1, MR/R020973/1) and BBSRC UK (BB/R013063/1). SC received funding from the Medical Research Council UK grants (MR/R020973/1) and the BBSRC UK (BB/R013063/1). JPhe is funded by the Medical Research Council UK grants (MR/S03563X/1).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSci Rep. 2020 Feb 13;10(1):2600. doi: 10.1038/s41598-020-59558-3pt_PT
dc.identifier.doi10.1038/s41598-020-59558-3pt_PT
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10400.18/7610
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Researchpt_PT
dc.relationResearch Institute for Medicines
dc.relationTargeting efflux pumps in drug resistant Mycobacterium tuberculosis: an approach to prevent efflux-mediated resistance and boost therapy in active and latent tuberculosis
dc.relationGlobal Health and Tropical Medicine
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-020-59558-3pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectExtensively Drug-Resistant Tuberculosispt_PT
dc.subjectGenetic Variationpt_PT
dc.subjectHumanspt_PT
dc.subjectMycobacterium tuberculosispt_PT
dc.subjectPhylogenypt_PT
dc.subjectPolymorphism, Single Nucleotidept_PT
dc.subjectPortugalpt_PT
dc.subjectWhole Genome Sequencingpt_PT
dc.subjectGenome, Bacterialpt_PT
dc.subjectInfecções Respiratóriaspt_PT
dc.titleUsing genomics to understand the origin and dispersion of multidrug and extensively drug resistant tuberculosis in Portugalpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleTargeting efflux pumps in drug resistant Mycobacterium tuberculosis: an approach to prevent efflux-mediated resistance and boost therapy in active and latent tuberculosis
oaire.awardTitleGlobal Health and Tropical Medicine
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FDTP%2F04138%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-MIC%2F30692%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04413%2F2013/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage2600pt_PT
oaire.citation.titleScientific Reportspt_PT
oaire.citation.volume10pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication206cdeaa-76a3-43a8-81c3-589822c1adb5
relation.isProjectOfPublication41c1e20d-6cd4-46c2-9725-ba0fe2fd9697
relation.isProjectOfPublication4b506a1b-3ea9-41d3-9221-3ad5eefbb9f6
relation.isProjectOfPublication.latestForDiscovery41c1e20d-6cd4-46c2-9725-ba0fe2fd9697

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