Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain

Autores
Bigi, María Mercedes; López, Beatriz; Blanco, Federico Carlos; Sasiain, María del Carmen; De La Barrera, Silvia Susana; Marti, Marcelo Adrián; Sosa, Ezequiel Jorge; Fernandez Do Porto, Darío Augusto; Ritacco, Viviana; Bigi, Fabiana; Soria, Marcelo Abel
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
Descripción
Globally, about 4.5% of new tuberculosis (TB) cases are multi-drug-resistant (MDR), i.e. resistant to the two most powerful first-line anti-TB drugs. Indeed, 480,000 people developed MDR-TB in 2015 and 190,000 people died because of MDR-TB. The MDR Mycobacterium tuberculosis M family, which belongs to the Haarlem lineage, is highly prosperous in Argentina and capable of building up further drug resistance without impairing its ability to spread. In this study, we sequenced the whole genomes of a highly prosperous M-family strain (Mp) and its contemporary variant, strain 410, which produced only one recorded tuberculosis case in the last two decades. Previous reports have demonstrated that Mp induced dysfunctional CD8þ cytotoxic T cell activity, suggesting that this strain has the ability to evade the immune response against M. tuberculosis. Comparative analysis of Mp and 410 genomes revealed non-synonymous polymorphisms in eleven genes and five intergenic regions with polymorphisms between both strains. Some of these genes and promoter regions are involved in the metabolism of cell wall components, others in drug resistance and a SNP in Rv1861, a gene encoding a putative transglycosylase that produces a truncated protein in Mp. The mutation in Rv3787c, a putative S-adenosyl-L methioninedependent methyltransferase, is conserved in all of the other prosperous M strains here analysed and absent in non-prosperous M strains. Remarkably, three polymorphic promoter regions displayed differential transcriptional activity between Mp and 410. We speculate that the observed mutations/polymorphisms are associated with the reported higher capacity of Mp for modulating the host's immune response.
Inst. de Biotecnología
Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Cátedra de de Microbiología; Argentina
Fil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Marti, Marcelo Adrian. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Sosa, Ezequiel Jorge. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; Argentina
Fil: Fernandez Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; Argentina
Fil: Ritacco, Viviana. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola; Argentina
Fuente
Tuberculosis 103 : 28-36. (December 28, 2016)
Materia
Mycobacterium tuberculosis
Polimorfismo
Nucleótidos
Fenotipos
Polymorphism
Nucleotides
Phenotypes
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/967
Acceder
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oai_identifier_str oai:localhost:20.500.12123/967
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network_name_str INTA Digital (INTA)
spelling Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strainBigi, María MercedesLópez, BeatrizBlanco, Federico CarlosSasiain, María del CarmenDe La Barrera, Silvia SusanaMarti, Marcelo AdriánSosa, Ezequiel JorgeFernandez Do Porto, Darío AugustoRitacco, VivianaBigi, FabianaSoria, Marcelo AbelMycobacterium tuberculosisPolimorfismoNucleótidosFenotiposPolymorphismNucleotidesPhenotypesGlobally, about 4.5% of new tuberculosis (TB) cases are multi-drug-resistant (MDR), i.e. resistant to the two most powerful first-line anti-TB drugs. Indeed, 480,000 people developed MDR-TB in 2015 and 190,000 people died because of MDR-TB. The MDR Mycobacterium tuberculosis M family, which belongs to the Haarlem lineage, is highly prosperous in Argentina and capable of building up further drug resistance without impairing its ability to spread. In this study, we sequenced the whole genomes of a highly prosperous M-family strain (Mp) and its contemporary variant, strain 410, which produced only one recorded tuberculosis case in the last two decades. Previous reports have demonstrated that Mp induced dysfunctional CD8þ cytotoxic T cell activity, suggesting that this strain has the ability to evade the immune response against M. tuberculosis. Comparative analysis of Mp and 410 genomes revealed non-synonymous polymorphisms in eleven genes and five intergenic regions with polymorphisms between both strains. Some of these genes and promoter regions are involved in the metabolism of cell wall components, others in drug resistance and a SNP in Rv1861, a gene encoding a putative transglycosylase that produces a truncated protein in Mp. The mutation in Rv3787c, a putative S-adenosyl-L methioninedependent methyltransferase, is conserved in all of the other prosperous M strains here analysed and absent in non-prosperous M strains. Remarkably, three polymorphic promoter regions displayed differential transcriptional activity between Mp and 410. We speculate that the observed mutations/polymorphisms are associated with the reported higher capacity of Mp for modulating the host's immune response.Inst. de BiotecnologíaFil: Bigi, María Mercedes. Universidad de Buenos Aires. Cátedra de de Microbiología; ArgentinaFil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; ArgentinaFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Marti, Marcelo Adrian. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Sosa, Ezequiel Jorge. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; ArgentinaFil: Fernandez Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; ArgentinaFil: Ritacco, Viviana. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; ArgentinaFil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola; Argentina2017-08-15T12:07:48Z2017-08-15T12:07:48Z2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/967http://www.tuberculosisjournal.com/article/S1472-9792(16)30366-3/fulltext1472-97921873-281X (Online)https://doi.org/10.1016/j.tube.2016.12.007Tuberculosis 103 : 28-36. (December 28, 2016)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccess2025-09-04T09:46:57Zoai:localhost:20.500.12123/967instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:46:58.301INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
title Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
spellingShingle Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
Bigi, María Mercedes
Mycobacterium tuberculosis
Polimorfismo
Nucleótidos
Fenotipos
Polymorphism
Nucleotides
Phenotypes
title_short Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
title_full Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
title_fullStr Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
title_full_unstemmed Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
title_sort Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
dc.creator.none.fl_str_mv Bigi, María Mercedes
López, Beatriz
Blanco, Federico Carlos
Sasiain, María del Carmen
De La Barrera, Silvia Susana
Marti, Marcelo Adrián
Sosa, Ezequiel Jorge
Fernandez Do Porto, Darío Augusto
Ritacco, Viviana
Bigi, Fabiana
Soria, Marcelo Abel
author Bigi, María Mercedes
author_facet Bigi, María Mercedes
López, Beatriz
Blanco, Federico Carlos
Sasiain, María del Carmen
De La Barrera, Silvia Susana
Marti, Marcelo Adrián
Sosa, Ezequiel Jorge
Fernandez Do Porto, Darío Augusto
Ritacco, Viviana
Bigi, Fabiana
Soria, Marcelo Abel
author_role author
author2 López, Beatriz
Blanco, Federico Carlos
Sasiain, María del Carmen
De La Barrera, Silvia Susana
Marti, Marcelo Adrián
Sosa, Ezequiel Jorge
Fernandez Do Porto, Darío Augusto
Ritacco, Viviana
Bigi, Fabiana
Soria, Marcelo Abel
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mycobacterium tuberculosis
Polimorfismo
Nucleótidos
Fenotipos
Polymorphism
Nucleotides
Phenotypes
topic Mycobacterium tuberculosis
Polimorfismo
Nucleótidos
Fenotipos
Polymorphism
Nucleotides
Phenotypes
dc.description.none.fl_txt_mv Globally, about 4.5% of new tuberculosis (TB) cases are multi-drug-resistant (MDR), i.e. resistant to the two most powerful first-line anti-TB drugs. Indeed, 480,000 people developed MDR-TB in 2015 and 190,000 people died because of MDR-TB. The MDR Mycobacterium tuberculosis M family, which belongs to the Haarlem lineage, is highly prosperous in Argentina and capable of building up further drug resistance without impairing its ability to spread. In this study, we sequenced the whole genomes of a highly prosperous M-family strain (Mp) and its contemporary variant, strain 410, which produced only one recorded tuberculosis case in the last two decades. Previous reports have demonstrated that Mp induced dysfunctional CD8þ cytotoxic T cell activity, suggesting that this strain has the ability to evade the immune response against M. tuberculosis. Comparative analysis of Mp and 410 genomes revealed non-synonymous polymorphisms in eleven genes and five intergenic regions with polymorphisms between both strains. Some of these genes and promoter regions are involved in the metabolism of cell wall components, others in drug resistance and a SNP in Rv1861, a gene encoding a putative transglycosylase that produces a truncated protein in Mp. The mutation in Rv3787c, a putative S-adenosyl-L methioninedependent methyltransferase, is conserved in all of the other prosperous M strains here analysed and absent in non-prosperous M strains. Remarkably, three polymorphic promoter regions displayed differential transcriptional activity between Mp and 410. We speculate that the observed mutations/polymorphisms are associated with the reported higher capacity of Mp for modulating the host's immune response.
Inst. de Biotecnología
Fil: Bigi, María Mercedes. Universidad de Buenos Aires. Cátedra de de Microbiología; Argentina
Fil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina
Fil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: de la Barrera, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Marti, Marcelo Adrian. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Sosa, Ezequiel Jorge. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; Argentina
Fil: Fernandez Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; Argentina
Fil: Ritacco, Viviana. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina
Fil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
Fil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola; Argentina
description Globally, about 4.5% of new tuberculosis (TB) cases are multi-drug-resistant (MDR), i.e. resistant to the two most powerful first-line anti-TB drugs. Indeed, 480,000 people developed MDR-TB in 2015 and 190,000 people died because of MDR-TB. The MDR Mycobacterium tuberculosis M family, which belongs to the Haarlem lineage, is highly prosperous in Argentina and capable of building up further drug resistance without impairing its ability to spread. In this study, we sequenced the whole genomes of a highly prosperous M-family strain (Mp) and its contemporary variant, strain 410, which produced only one recorded tuberculosis case in the last two decades. Previous reports have demonstrated that Mp induced dysfunctional CD8þ cytotoxic T cell activity, suggesting that this strain has the ability to evade the immune response against M. tuberculosis. Comparative analysis of Mp and 410 genomes revealed non-synonymous polymorphisms in eleven genes and five intergenic regions with polymorphisms between both strains. Some of these genes and promoter regions are involved in the metabolism of cell wall components, others in drug resistance and a SNP in Rv1861, a gene encoding a putative transglycosylase that produces a truncated protein in Mp. The mutation in Rv3787c, a putative S-adenosyl-L methioninedependent methyltransferase, is conserved in all of the other prosperous M strains here analysed and absent in non-prosperous M strains. Remarkably, three polymorphic promoter regions displayed differential transcriptional activity between Mp and 410. We speculate that the observed mutations/polymorphisms are associated with the reported higher capacity of Mp for modulating the host's immune response.
publishDate 2017
dc.date.none.fl_str_mv 2017-08-15T12:07:48Z
2017-08-15T12:07:48Z
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/967
http://www.tuberculosisjournal.com/article/S1472-9792(16)30366-3/fulltext
1472-9792
1873-281X (Online)
https://doi.org/10.1016/j.tube.2016.12.007
url http://hdl.handle.net/20.500.12123/967
http://www.tuberculosisjournal.com/article/S1472-9792(16)30366-3/fulltext
https://doi.org/10.1016/j.tube.2016.12.007
identifier_str_mv 1472-9792
1873-281X (Online)
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
eu_rights_str_mv restrictedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Tuberculosis 103 : 28-36. (December 28, 2016)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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