Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
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...
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| Format: | Artículo |
| Language: | Inglés |
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2017
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| Online Access: | 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 |
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| author | 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_browse | Bigi, Fabiana Bigi, María Mercedes Blanco, Federico Carlos De La Barrera, Silvia Susana Fernandez Do Porto, Darío Augusto López, Beatriz Marti, Marcelo Adrián Ritacco, Viviana Sasiain, María del Carmen Soria, Marcelo Abel Sosa, Ezequiel Jorge |
| 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_sort | Bigi, María Mercedes |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA967 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | INTA9672019-03-22T13:01:42Z Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain 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 Mycobacterium tuberculosis Polimorfismo Nucleótidos Fenotipos Polymorphism Nucleotides Phenotypes 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 2017-08-15T12:07:48Z 2017-08-15T12:07:48Z 2017 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 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 eng info:eu-repo/semantics/restrictedAccess application/pdf Tuberculosis 103 : 28-36. (December 28, 2016) |
| spellingShingle | Mycobacterium tuberculosis Polimorfismo Nucleótidos Fenotipos Polymorphism Nucleotides Phenotypes 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 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 |
| 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_short | 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 |
| topic | Mycobacterium tuberculosis Polimorfismo Nucleótidos Fenotipos Polymorphism Nucleotides Phenotypes |
| 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 |
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