Genomic diversity of drug-resistant Mycobacterium tuberculosis isolates in Lisbon Portugal: Towards tuberculosis genomic epidemiology

Handle URI:
http://hdl.handle.net/10754/348484
Title:
Genomic diversity of drug-resistant Mycobacterium tuberculosis isolates in Lisbon Portugal: Towards tuberculosis genomic epidemiology
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:
Multidrug- (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) present a challenge to disease control and elimination goals. Lisbon, Portugal, has a high TB incidence rate and unusual and successful XDR-TB strains that have been found in circulation for almost two decades. For the last 20. years, a continued circulation of two phylogenetic clades, Lisboa3 and Q1, which are highly associated with MDR and XDR, have been observed. In recent years, these strains have been well characterized regarding the molecular basis of drug resistance and have been inclusively subjected to whole genome sequencing (WGS). Researchers have been studying the genomic diversity of strains circulating in Lisbon and its genomic determinants through cutting-edge next generation sequencing. An enormous amount of whole genome sequence data are now available for the most prevalent and clinically relevant strains circulating in Lisbon.It is the persistence, prevalence and rapid evolution towards drug resistance that has prompted researchers to investigate the properties of these strains at the genomic level and in the future at a global transcriptomic level. Seventy Mycobacterium tuberculosis (MTB) isolates, mostly recovered in Lisbon, were genotyped by 24-. loci Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeats (MIRU-VNTR) and the genomes sequenced using a next generation sequencing platform - Illumina HiSeq 2000.The genotyping data revealed three major clusters associated with MDR-TB (Lisboa3-A, Lisboa3-B and Q1), two of which are associated with XDR-TB (Lisboa3-B and Q1), whilst the genomic data contributed to elucidating 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 MTB clinical isolates, revealed two major clades responsible for MDR/XDR-TB in the region: Lisboa3 and Q1. The data presented by this study contributes to the expanding knowledge of MTB genomic diversity yielding insights on microevolution and identification of novel compensatory mutations. Additionally, the analysis of non-synonymous/synonymous ratios revealed heterogeneities across the chromosome, genotype and Clusters of Orthologous Groups, highlighting possible and different evolution strategies. Overall, the results that are presented support the notion of an increasing genomic diversity that may support both setting and host adaptation.
KAUST Department:
Pathogen Genomics Laboratory
Citation:
Genomic diversity of drug-resistant Mycobacterium tuberculosis isolates in Lisbon Portugal: Towards tuberculosis genomic epidemiology 2015, 4:27 International Journal of Mycobacteriology
Publisher:
Elsevier BV
Journal:
International Journal of Mycobacteriology
Issue Date:
Mar-2015
DOI:
10.1016/j.ijmyco.2015.01.001
Type:
Abstract
ISSN:
22125531
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S2212553115000254
Appears in Collections:
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 G.en
dc.contributor.authorViveiros, Miguelen
dc.contributor.authorPortugal, Isabelen
dc.date.accessioned2015-04-02T13:45:06Zen
dc.date.available2015-04-02T13:45:06Zen
dc.date.issued2015-03en
dc.identifier.citationGenomic diversity of drug-resistant Mycobacterium tuberculosis isolates in Lisbon Portugal: Towards tuberculosis genomic epidemiology 2015, 4:27 International Journal of Mycobacteriologyen
dc.identifier.issn22125531en
dc.identifier.doi10.1016/j.ijmyco.2015.01.001en
dc.identifier.urihttp://hdl.handle.net/10754/348484en
dc.description.abstractMultidrug- (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) present a challenge to disease control and elimination goals. Lisbon, Portugal, has a high TB incidence rate and unusual and successful XDR-TB strains that have been found in circulation for almost two decades. For the last 20. years, a continued circulation of two phylogenetic clades, Lisboa3 and Q1, which are highly associated with MDR and XDR, have been observed. In recent years, these strains have been well characterized regarding the molecular basis of drug resistance and have been inclusively subjected to whole genome sequencing (WGS). Researchers have been studying the genomic diversity of strains circulating in Lisbon and its genomic determinants through cutting-edge next generation sequencing. An enormous amount of whole genome sequence data are now available for the most prevalent and clinically relevant strains circulating in Lisbon.It is the persistence, prevalence and rapid evolution towards drug resistance that has prompted researchers to investigate the properties of these strains at the genomic level and in the future at a global transcriptomic level. Seventy Mycobacterium tuberculosis (MTB) isolates, mostly recovered in Lisbon, were genotyped by 24-. loci Mycobacterial Interspersed Repetitive Unit - Variable Number of Tandem Repeats (MIRU-VNTR) and the genomes sequenced using a next generation sequencing platform - Illumina HiSeq 2000.The genotyping data revealed three major clusters associated with MDR-TB (Lisboa3-A, Lisboa3-B and Q1), two of which are associated with XDR-TB (Lisboa3-B and Q1), whilst the genomic data contributed to elucidating 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 MTB clinical isolates, revealed two major clades responsible for MDR/XDR-TB in the region: Lisboa3 and Q1. The data presented by this study contributes to the expanding knowledge of MTB genomic diversity yielding insights on microevolution and identification of novel compensatory mutations. Additionally, the analysis of non-synonymous/synonymous ratios revealed heterogeneities across the chromosome, genotype and Clusters of Orthologous Groups, highlighting possible and different evolution strategies. Overall, the results that are presented support the notion of an increasing genomic diversity that may support both setting and host adaptation.en
dc.publisherElsevier BVen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S2212553115000254en
dc.rightsArchived with thanks to International Journal of Mycobacteriology. http://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.titleGenomic diversity of drug-resistant Mycobacterium tuberculosis isolates in Lisbon Portugal: Towards tuberculosis genomic epidemiologyen
dc.typeAbstracten
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.identifier.journalInternational Journal of Mycobacteriologyen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCentro de Patogénese Molecular, URIA, Faculdade de Farmácia da Universidade de 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 Laboratory: Mycobacteriology/Tuberculosis, Public Health Department, 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, 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, NSW 2006, Australiaen
kaust.authorHill-Cawthorne, Grant A.en
kaust.authorPain, Arnaben
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