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Using Genomics to Understand the Origin and Dispersion of Multidrug and Extensively Drug Resistant Tuberculosis in Portugal

2020Journal article Open access
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dc.contributor.authorPerdigão, J
dc.contributor.authorGomes, P
dc.contributor.authorMiranda, A
dc.contributor.authorMaltez, F
dc.contributor.authorMachado, D
dc.contributor.authorSilva, C
dc.contributor.authorPhelan, J
dc.contributor.authorBrum, L
dc.contributor.authorCampino, S
dc.contributor.authorCouto, I
dc.contributor.authorViveiros, M
dc.contributor.authorClark, T
dc.contributor.authorPortugal, I
dc.date.accessioned2021-11-10T16:09:27Z
dc.date.available2021-11-10T16:09:27Z
dc.date.issued2020
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.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSci Rep. 2020 Feb 13;10(1):2600.pt_PT
dc.identifier.doi10.1038/s41598-020-59558-3.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3897
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.subjectHCC INFpt_PT
dc.subjectExtensively Drug-Resistant Tuberculosis / epidemiology*pt_PT
dc.subjectExtensively Drug-Resistant Tuberculosis / microbiology*pt_PT
dc.subjectGenetic Variationpt_PT
dc.subjectHumanspt_PT
dc.subjectGenome, Bacterial*pt_PT
dc.subjectMycobacterium tuberculosis / genetics*pt_PT
dc.subjectMycobacterium tuberculosis / isolation & purificationpt_PT
dc.subjectPhylogenypt_PT
dc.subjectPolymorphism, Single Nucleotidept_PT
dc.subjectPortugal / epidemiologypt_PT
dc.subjectWhole Genome Sequencingpt_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.citation.startPage2600pt_PT
oaire.citation.titleScientific Reportspt_PT
oaire.citation.volume10pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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