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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 [ver mas...]
dc.contributor.authorBigi, María Mercedes
dc.contributor.authorLópez, Beatriz
dc.contributor.authorBlanco, Federico Carlos
dc.contributor.authorSasiain, María del Carmen
dc.contributor.authorDe La Barrera, Silvia Susana
dc.contributor.authorMarti, Marcelo Adrián
dc.contributor.authorSosa, Ezequiel Jorge
dc.contributor.authorFernandez Do Porto, Darío Augusto
dc.contributor.authorRitacco, Viviana
dc.contributor.authorBigi, Fabiana
dc.contributor.authorSoria, Marcelo Abel
dc.date.accessioned2017-08-15T12:07:48Z
dc.date.available2017-08-15T12:07:48Z
dc.date.issued2017
dc.identifier.issn1472-9792
dc.identifier.issn1873-281X (Online)
dc.identifier.otherhttps://doi.org/10.1016/j.tube.2016.12.007
dc.identifier.urihttp://hdl.handle.net/20.500.12123/967
dc.identifier.urihttp://www.tuberculosisjournal.com/article/S1472-9792(16)30366-3/fulltext
dc.description.abstractGlobally, 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.
dc.formatapplication/pdfeng
dc.language.isoeng
dc.rightsinfo:eu-repo/semantics/restrictedAccesseng
dc.sourceTuberculosis 103 : 28-36. (December 28, 2016)
dc.subjectMycobacterium tuberculosis
dc.subjectPolymorphismeng
dc.subjectPolimorfismo
dc.subjectNucleotideseng
dc.subjectNucleótidos
dc.subjectFenotipos
dc.subjectPhenotypeseng
dc.titleSingle nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis straineng
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/articleeng
dc.typeinfo:eu-repo/semantics/acceptedVersioneng
dc.description.origenInst. de Biotecnología
dc.gic152951
dc.description.filFil: Bigi, María Mercedes. Universidad de Buenos Aires. Cátedra de de Microbiología; Argentina
dc.description.filFil: López, Beatriz. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina
dc.description.filFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
dc.description.filFil: 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
dc.description.filFil: 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
dc.description.filFil: 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
dc.description.filFil: Sosa, Ezequiel Jorge. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; Argentina
dc.description.filFil: Fernandez Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina; Argentina
dc.description.filFil: Ritacco, Viviana. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas “Dr. Carlos G. Malbrán”; Argentina
dc.description.filFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina
dc.description.filFil: Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola; Argentina
dc.subtypecientifico


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