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

Colaborador(es): Bigi, María Mercedes. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola. Buenos Aires, Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales (INBA). Buenos Aires, Argentina. CONICET - Universidad de Buenos Aires. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales (INBA). uenos Aires, Argentina | López, Beatríz. Instituto Nacional de Enfermedades Infecciosas (ANLIS) Carlos Malbrán. Buenos Aires, Argentina | Blanco, Federico C. Instituto Nacional de Tecnología Agropecuaria (INTA). Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología. Hurlingham, Buenos Aires, Argentina | Sasiain, María del Carmen. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX). Buenos Aires, Argentina. CONICET. Buenos Aires, Argentina | Barrera, Silvia de la. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX). Buenos Aires, Argentina. CONICET. Buenos Aires, Argentina | Marti, Marcelo A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Buenos Aires, Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Buenos Aires, Argentina. CONICET - Universidad de Buenos Aires. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Buenos Aires, Argentina | Sosa, Ezequiel Jorge. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina (BIA). Buenos Aires, Argentina | Fernández Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina (BIA). Buenos Aires, Argentina | Ritacco, Viviana. Instituto Nacional de Enfermedades Infecciosas (ANLIS) Carlos Malbrán. Buenos Aires, Argentina | Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología. Hurlingham, Buenos Aires, Argentina | Soria, Marcelo Abel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Microbiología Agrícola. Buenos Aires, Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales (INBA). Buenos Aires, Argentina. CONICET - Universidad de Buenos Aires. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales (INBA). uenos Aires, Argentina.
ISSN: 1472-9792.Tipo de material: Artículos y capítulos. Recurso electrónico.Tema(s): MYCOBACTERIUM TUBERCULOSIS | MDR | HAARLEM | GENOME SEQUENCING | POLYMORPHISMS | Recursos en línea: Haga clic para acceso en línea | LINK AL EDITOR En: Tuberculosis Vol.103 (2017), p.28-36, grafs., tbls.Resumen: Globally, about 4.5% of new tuberculosis (TB) cases are multidrug-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- -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.
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Globally, about 4.5% of new tuberculosis (TB) cases are multidrug-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- -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.

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