Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development

Autores
Cubillos Ruiz, Andrés; Sandoval, Andrea; Ritacco, Gloria Viviana; López, Beatriz Graciela; Robledo, Jaime; Correa, Nidia; Hernandez-Neuta, Iván; Zambrano, Maria Mercedes; Del Portillo, Patricia
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Tuberculosis is the world's leading cause of death due to a single infectious agent, and efforts aimed at its control require a better understanding of host, environmental, and bacterial factors that govern disease outcome. Growing evidence indicates that certain Mycobacterium tuberculosis strains of distinct phylogeographic lineages elicit unique immunopathological events. However, identifying the genetic basis of these phenotypic peculiarities has proven difficult. Here we report the presence of six large sequence polymorphisms which, together with two single-nucleotide changes previously described by our group, consistently differentiate Haarlem strains from the remaining M. tuberculosis lineages. The six newly found Haarlem-specific genetic events are four deletions, which altogether involve more than 13 kb, and two intragenic insertions of the element IS6110. The absence of the genes involved in these polymorphisms could have an important physiological impact on Haarlem strains, i.e., by affecting key genes, such as Rv1354c and cyp121, which have been recently proposed as plausible drug targets. These lineage-specific polymorphisms can serve as genetic markers for the rapid PCR identification of Haarlem strains, providing a useful tool for strain surveillance and molecular epidemiology studies. Strain variability such as that described here underscores the need for the definition of a core set of essential genes in M. tuberculosis that are ubiquitously present in all circulating lineages, as a requirement in the development of effective antituberculosis drugs and vaccines.
Fil: Cubillos Ruiz, Andrés. Corporación Corpogen; Colombia
Fil: Sandoval, Andrea. Corporación Corpogen; Colombia
Fil: Ritacco, Gloria Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: López, Beatriz Graciela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: Robledo, Jaime. Centro Colombiano de Investigación En Tuberculosis; Colombia. Universidad Pontificia Bolivariana; Colombia
Fil: Correa, Nidia. Centro Colombiano de Investigación En Tuberculosis; Colombia. Universidad Pontificia Bolivariana; Colombia
Fil: Hernandez-Neuta, Iván. Corporación Corpogen; Colombia
Fil: Zambrano, Maria Mercedes. Corporación Corpogen; Colombia
Fil: Del Portillo, Patricia. Corporación Corpogen; Colombia. Centro Colombiano de Investigación En Tuberculosis; Colombia
Materia
GENETICS
MYCOBACTERIUM TUBERCULOSIS
HAARLEM LINEAGE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/190893
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/190893
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine developmentCubillos Ruiz, AndrésSandoval, AndreaRitacco, Gloria VivianaLópez, Beatriz GracielaRobledo, JaimeCorrea, NidiaHernandez-Neuta, IvánZambrano, Maria MercedesDel Portillo, PatriciaGENETICSMYCOBACTERIUM TUBERCULOSISHAARLEM LINEAGEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Tuberculosis is the world's leading cause of death due to a single infectious agent, and efforts aimed at its control require a better understanding of host, environmental, and bacterial factors that govern disease outcome. Growing evidence indicates that certain Mycobacterium tuberculosis strains of distinct phylogeographic lineages elicit unique immunopathological events. However, identifying the genetic basis of these phenotypic peculiarities has proven difficult. Here we report the presence of six large sequence polymorphisms which, together with two single-nucleotide changes previously described by our group, consistently differentiate Haarlem strains from the remaining M. tuberculosis lineages. The six newly found Haarlem-specific genetic events are four deletions, which altogether involve more than 13 kb, and two intragenic insertions of the element IS6110. The absence of the genes involved in these polymorphisms could have an important physiological impact on Haarlem strains, i.e., by affecting key genes, such as Rv1354c and cyp121, which have been recently proposed as plausible drug targets. These lineage-specific polymorphisms can serve as genetic markers for the rapid PCR identification of Haarlem strains, providing a useful tool for strain surveillance and molecular epidemiology studies. Strain variability such as that described here underscores the need for the definition of a core set of essential genes in M. tuberculosis that are ubiquitously present in all circulating lineages, as a requirement in the development of effective antituberculosis drugs and vaccines.Fil: Cubillos Ruiz, Andrés. Corporación Corpogen; ColombiaFil: Sandoval, Andrea. Corporación Corpogen; ColombiaFil: Ritacco, Gloria Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: López, Beatriz Graciela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Robledo, Jaime. Centro Colombiano de Investigación En Tuberculosis; Colombia. Universidad Pontificia Bolivariana; ColombiaFil: Correa, Nidia. Centro Colombiano de Investigación En Tuberculosis; Colombia. Universidad Pontificia Bolivariana; ColombiaFil: Hernandez-Neuta, Iván. Corporación Corpogen; ColombiaFil: Zambrano, Maria Mercedes. Corporación Corpogen; ColombiaFil: Del Portillo, Patricia. Corporación Corpogen; Colombia. Centro Colombiano de Investigación En Tuberculosis; ColombiaAmerican Society for Microbiology2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/190893Cubillos Ruiz, Andrés; Sandoval, Andrea; Ritacco, Gloria Viviana; López, Beatriz Graciela; Robledo, Jaime; et al.; Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development; American Society for Microbiology; Journal of Clinical Microbiology; 48; 10; 10-2010; 3614-36230095-1137CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/JCM.00157-10info:eu-repo/semantics/altIdentifier/doi/10.1128/JCM.00157-10info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:07Zoai:ri.conicet.gov.ar:11336/190893instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:38:07.895CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
title Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
spellingShingle Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
Cubillos Ruiz, Andrés
GENETICS
MYCOBACTERIUM TUBERCULOSIS
HAARLEM LINEAGE
title_short Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
title_full Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
title_fullStr Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
title_full_unstemmed Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
title_sort Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development
dc.creator.none.fl_str_mv Cubillos Ruiz, Andrés
Sandoval, Andrea
Ritacco, Gloria Viviana
López, Beatriz Graciela
Robledo, Jaime
Correa, Nidia
Hernandez-Neuta, Iván
Zambrano, Maria Mercedes
Del Portillo, Patricia
author Cubillos Ruiz, Andrés
author_facet Cubillos Ruiz, Andrés
Sandoval, Andrea
Ritacco, Gloria Viviana
López, Beatriz Graciela
Robledo, Jaime
Correa, Nidia
Hernandez-Neuta, Iván
Zambrano, Maria Mercedes
Del Portillo, Patricia
author_role author
author2 Sandoval, Andrea
Ritacco, Gloria Viviana
López, Beatriz Graciela
Robledo, Jaime
Correa, Nidia
Hernandez-Neuta, Iván
Zambrano, Maria Mercedes
Del Portillo, Patricia
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GENETICS
MYCOBACTERIUM TUBERCULOSIS
HAARLEM LINEAGE
topic GENETICS
MYCOBACTERIUM TUBERCULOSIS
HAARLEM LINEAGE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Tuberculosis is the world's leading cause of death due to a single infectious agent, and efforts aimed at its control require a better understanding of host, environmental, and bacterial factors that govern disease outcome. Growing evidence indicates that certain Mycobacterium tuberculosis strains of distinct phylogeographic lineages elicit unique immunopathological events. However, identifying the genetic basis of these phenotypic peculiarities has proven difficult. Here we report the presence of six large sequence polymorphisms which, together with two single-nucleotide changes previously described by our group, consistently differentiate Haarlem strains from the remaining M. tuberculosis lineages. The six newly found Haarlem-specific genetic events are four deletions, which altogether involve more than 13 kb, and two intragenic insertions of the element IS6110. The absence of the genes involved in these polymorphisms could have an important physiological impact on Haarlem strains, i.e., by affecting key genes, such as Rv1354c and cyp121, which have been recently proposed as plausible drug targets. These lineage-specific polymorphisms can serve as genetic markers for the rapid PCR identification of Haarlem strains, providing a useful tool for strain surveillance and molecular epidemiology studies. Strain variability such as that described here underscores the need for the definition of a core set of essential genes in M. tuberculosis that are ubiquitously present in all circulating lineages, as a requirement in the development of effective antituberculosis drugs and vaccines.
Fil: Cubillos Ruiz, Andrés. Corporación Corpogen; Colombia
Fil: Sandoval, Andrea. Corporación Corpogen; Colombia
Fil: Ritacco, Gloria Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: López, Beatriz Graciela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentina
Fil: Robledo, Jaime. Centro Colombiano de Investigación En Tuberculosis; Colombia. Universidad Pontificia Bolivariana; Colombia
Fil: Correa, Nidia. Centro Colombiano de Investigación En Tuberculosis; Colombia. Universidad Pontificia Bolivariana; Colombia
Fil: Hernandez-Neuta, Iván. Corporación Corpogen; Colombia
Fil: Zambrano, Maria Mercedes. Corporación Corpogen; Colombia
Fil: Del Portillo, Patricia. Corporación Corpogen; Colombia. Centro Colombiano de Investigación En Tuberculosis; Colombia
description Tuberculosis is the world's leading cause of death due to a single infectious agent, and efforts aimed at its control require a better understanding of host, environmental, and bacterial factors that govern disease outcome. Growing evidence indicates that certain Mycobacterium tuberculosis strains of distinct phylogeographic lineages elicit unique immunopathological events. However, identifying the genetic basis of these phenotypic peculiarities has proven difficult. Here we report the presence of six large sequence polymorphisms which, together with two single-nucleotide changes previously described by our group, consistently differentiate Haarlem strains from the remaining M. tuberculosis lineages. The six newly found Haarlem-specific genetic events are four deletions, which altogether involve more than 13 kb, and two intragenic insertions of the element IS6110. The absence of the genes involved in these polymorphisms could have an important physiological impact on Haarlem strains, i.e., by affecting key genes, such as Rv1354c and cyp121, which have been recently proposed as plausible drug targets. These lineage-specific polymorphisms can serve as genetic markers for the rapid PCR identification of Haarlem strains, providing a useful tool for strain surveillance and molecular epidemiology studies. Strain variability such as that described here underscores the need for the definition of a core set of essential genes in M. tuberculosis that are ubiquitously present in all circulating lineages, as a requirement in the development of effective antituberculosis drugs and vaccines.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/190893
Cubillos Ruiz, Andrés; Sandoval, Andrea; Ritacco, Gloria Viviana; López, Beatriz Graciela; Robledo, Jaime; et al.; Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development; American Society for Microbiology; Journal of Clinical Microbiology; 48; 10; 10-2010; 3614-3623
0095-1137
CONICET Digital
CONICET
url http://hdl.handle.net/11336/190893
identifier_str_mv Cubillos Ruiz, Andrés; Sandoval, Andrea; Ritacco, Gloria Viviana; López, Beatriz Graciela; Robledo, Jaime; et al.; Genomic signatures of the Haarlem lineage of Mycobacterium tuberculosis: Implications of strain genetic variation in drug and vaccine development; American Society for Microbiology; Journal of Clinical Microbiology; 48; 10; 10-2010; 3614-3623
0095-1137
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/JCM.00157-10
info:eu-repo/semantics/altIdentifier/doi/10.1128/JCM.00157-10
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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