Artículo

Bigi, M.M.; Lopez, B.; Blanco, F.C.; Sasiain, M.D.C.; De la Barrera, S.; Marti, M.A.; Sosa, E.J.; Fernández Do Porto, D.A.; Ritacco, V.; Bigi, F.; Soria, M.A. "Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain" (2017) Tuberculosis. 103:28-36
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Abstract:

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 CD8 + 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-methionine-dependent 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. © 2017 Elsevier Ltd

Registro:

Documento: Artículo
Título:Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
Autor:Bigi, M.M.; Lopez, B.; Blanco, F.C.; Sasiain, M.D.C.; De la Barrera, S.; Marti, M.A.; Sosa, E.J.; Fernández Do Porto, D.A.; Ritacco, V.; Bigi, F.; Soria, M.A.
Filiación:Universidad de Buenos Aires, Facultad de Agronomía, Cátedra de Microbiología Agrícola.INBA-CONICET, Av. San Martín 4453, Buenos Aires, C1417DSE, Argentina
Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Av. Vélez Sarsfield 563, Buenos Aires, C1282AFF, Argentina
Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria (INTA), N. Repetto and De los Reseros, Hurlingham, 1686, Buenos Aires, Argentina
IMEX-CONICET, Academia Nacional de Medicina, José Andrés Pacheco de Melo 3081, Buenos Aires, C1425AUM, Argentina
Departamento de Química Biológica, IQUIBICEN-CONICET, FCEyN, UBA, Intendente Güiraldes 2160, Buenos Aires, C1428EGA, Argentina
Plataforma de Bioinformática Argentina, Instituto de Cálculo, FCEyN, UBA, Intendente Güiraldes 2160, Buenos Aires, C1428EGA, Argentina
Palabras clave:Genome sequencing; Haarlem; MDR; Mycobacterium tuberculosis; Polymorphisms; CD8 antigen; glycosyltransferase; methyltransferase; s adenosyl methionine dependent methyltransferase; spacer DNA; unclassified drug; bacterial protein; tuberculostatic agent; Article; bacterial cell wall; bacterial gene; bacterial genome; bacterial metabolism; bacterial mutation; bacterial strain; CD8+ T lymphocyte; comparative study; controlled study; cytotoxic T lymphocyte; gene sequence; immune response; multidrug resistance; Mycobacterium tuberculosis; nonhuman; phenotype; priority journal; promoter region; sequence alignment; single nucleotide polymorphism; drug effects; gene expression regulation; genetics; genotype; host pathogen interaction; human; immunology; microbiology; multidrug resistance; multidrug resistant tuberculosis; mutation; Mycobacterium tuberculosis; pathogenicity; Antitubercular Agents; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Genome, Bacterial; Genotype; Host-Pathogen Interactions; Humans; Mutation; Mycobacterium tuberculosis; Phenotype; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Tuberculosis, Multidrug-Resistant
Año:2017
Volumen:103
Página de inicio:28
Página de fin:36
DOI: http://dx.doi.org/10.1016/j.tube.2016.12.007
Título revista:Tuberculosis
Título revista abreviado:Tuberculosis
ISSN:14729792
CODEN:TUBEC
CAS:glycosyltransferase, 9033-07-2; methyltransferase, 9033-25-4; Antitubercular Agents; Bacterial Proteins
Registro:http://digital.bl.fcen.uba.ar/collection/paper/document/paper_14729792_v103_n_p28_Bigi

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Citas:

---------- APA ----------
Bigi, M.M., Lopez, B., Blanco, F.C., Sasiain, M.D.C., De la Barrera, S., Marti, M.A., Sosa, E.J.,..., Soria, M.A. (2017) . Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain. Tuberculosis, 103, 28-36.
http://dx.doi.org/10.1016/j.tube.2016.12.007
---------- CHICAGO ----------
Bigi, M.M., Lopez, B., Blanco, F.C., Sasiain, M.D.C., De la Barrera, S., Marti, M.A., et al. "Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain" . Tuberculosis 103 (2017) : 28-36.
http://dx.doi.org/10.1016/j.tube.2016.12.007
---------- MLA ----------
Bigi, M.M., Lopez, B., Blanco, F.C., Sasiain, M.D.C., De la Barrera, S., Marti, M.A., et al. "Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain" . Tuberculosis, vol. 103, 2017, pp. 28-36.
http://dx.doi.org/10.1016/j.tube.2016.12.007
---------- VANCOUVER ----------
Bigi, M.M., Lopez, B., Blanco, F.C., Sasiain, M.D.C., De la Barrera, S., Marti, M.A., et al. Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain. Tuberculosis. 2017;103:28-36.
http://dx.doi.org/10.1016/j.tube.2016.12.007