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, Viviana; López, Beatriz; 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, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Robledo, Jaime. Universidad Pontificia Bolivariana. Corporación para Investigaciones Biológicas; Colombia.
Fil: Correa, Nidia. Universidad Pontificia Bolivariana. Corporación para Investigaciones Biológicas; Colombia.
Fil: Hernandez-Neuta, Iván. Corporación Corpogen; Colombia.
Fil: Zambrano, Maria Mercedes. Corporación Corpogen; Colombia.
Fil: Del Portillo, Patricia. Corporación Corpogen; Colombia.
Fuente
Journal of Clinical Microbiology, 2010, 48(10), 3614–3623.
Materia
Mycobacterium tuberculosis
Tuberculosis
Mutagénesis Insercional
Antituberculosos
Polimorfismo Genético
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Repositorio
Sistema de Gestión del Conocimiento ANLIS MALBRÁN
Institución
Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
OAI Identificador
oai:sgc.anlis.gob.ar:Publications/123456789/287
Acceder
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network_acronym_str SGCANLIS
repository_id_str a
network_name_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
spelling Genomic signatures of the haarlem lineage of Mycobacterium tuberculosis: implications of strain genetic variation in drug and vaccine developmentCubillos-Ruiz, AndrésSandoval, AndreaRitacco, VivianaLópez, BeatrizRobledo, JaimeCorrea, NidiaHernandez-Neuta, IvánZambrano, Maria MercedesDel Portillo, PatriciaMycobacterium tuberculosisTuberculosisMutagénesis InsercionalAntituberculososPolimorfismo GenéticoTuberculosis 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, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Robledo, Jaime. Universidad Pontificia Bolivariana. Corporación para Investigaciones Biológicas; Colombia.Fil: Correa, Nidia. Universidad Pontificia Bolivariana. Corporación para Investigaciones Biológicas; Colombia.Fil: Hernandez-Neuta, Iván. Corporación Corpogen; Colombia.Fil: Zambrano, Maria Mercedes. Corporación Corpogen; Colombia.Fil: Del Portillo, Patricia. Corporación Corpogen; Colombia.2010info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdf1098-660Xhttp://jcm.asm.org/content/48/10/3614.full.pdf+htmlhttp://sgc.anlis.gob.ar/handle/123456789/287Journal of Clinical Microbiology, 2010, 48(10), 3614–3623.reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLISenginfo:eu-repo/semantics/openAccess2025-10-16T10:11:09Zoai:sgc.anlis.gob.ar:Publications/123456789/287Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2025-10-16 10:11:09.831Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"false
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
Mycobacterium tuberculosis
Tuberculosis
Mutagénesis Insercional
Antituberculosos
Polimorfismo Genético
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, Viviana
López, Beatriz
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, Viviana
López, Beatriz
Robledo, Jaime
Correa, Nidia
Hernandez-Neuta, Iván
Zambrano, Maria Mercedes
Del Portillo, Patricia
author_role author
author2 Sandoval, Andrea
Ritacco, Viviana
López, Beatriz
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 Mycobacterium tuberculosis
Tuberculosis
Mutagénesis Insercional
Antituberculosos
Polimorfismo Genético
topic Mycobacterium tuberculosis
Tuberculosis
Mutagénesis Insercional
Antituberculosos
Polimorfismo Genético
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, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: López, Beatriz. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.
Fil: Robledo, Jaime. Universidad Pontificia Bolivariana. Corporación para Investigaciones Biológicas; Colombia.
Fil: Correa, Nidia. Universidad Pontificia Bolivariana. Corporación para Investigaciones Biológicas; Colombia.
Fil: Hernandez-Neuta, Iván. Corporación Corpogen; Colombia.
Fil: Zambrano, Maria Mercedes. Corporación Corpogen; Colombia.
Fil: Del Portillo, Patricia. Corporación Corpogen; 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
dc.type.none.fl_str_mv info:ar-repo/semantics/articulo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 1098-660X
http://jcm.asm.org/content/48/10/3614.full.pdf+html
http://sgc.anlis.gob.ar/handle/123456789/287
identifier_str_mv 1098-660X
url http://jcm.asm.org/content/48/10/3614.full.pdf+html
http://sgc.anlis.gob.ar/handle/123456789/287
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Journal of Clinical Microbiology, 2010, 48(10), 3614–3623.
reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron:ANLIS
reponame_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
collection Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname_str Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron_str ANLIS
institution ANLIS
repository.name.fl_str_mv Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
repository.mail.fl_str_mv biblioteca@anlis.gov.ar
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score 13.229304

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