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

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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...

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Autores principales:	Fernandez Do Porto, Dario Augusto, Bigi, Fabiana, Soria, Marcelo Abel
Publicado:	2017
Materias:	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 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 resistant tuberculosis mutation pathogenicity Antitubercular Agents Bacterial Proteins Drug Resistance, Multiple, Bacterial Gene Expression Regulation, Bacterial Genome, Bacterial Genotype Host-Pathogen Interactions Humans Mutation Phenotype Polymorphism, Single Nucleotide Promoter Regions, Genetic Tuberculosis, Multidrug-Resistant
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14729792_v103_n_p28_Bigi http://hdl.handle.net/20.500.12110/paper_14729792_v103_n_p28_Bigi
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_14729792_v103_n_p28_Bigi
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spelling	paper:paper_14729792_v103_n_p28_Bigi2023-06-08T16:17:32Z Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain Fernandez Do Porto, Dario Augusto Bigi, Fabiana Soria, Marcelo Abel 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 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 Fil:Fernández Do Porto, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bigi, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Soria, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14729792_v103_n_p28_Bigi http://hdl.handle.net/20.500.12110/paper_14729792_v103_n_p28_Bigi
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Fernandez Do Porto, Dario Augusto Bigi, Fabiana Soria, Marcelo Abel Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain
topic_facet	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
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 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
author	Fernandez Do Porto, Dario Augusto Bigi, Fabiana Soria, Marcelo Abel
author_facet	Fernandez Do Porto, Dario Augusto Bigi, Fabiana Soria, Marcelo Abel
author_sort	Fernandez Do Porto, Dario Augusto
title	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_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
publishDate	2017
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14729792_v103_n_p28_Bigi http://hdl.handle.net/20.500.12110/paper_14729792_v103_n_p28_Bigi
work_keys_str_mv	AT fernandezdoportodarioaugusto singlenucleotidepolymorphismsmayexplainthecontrastingphenotypesoftwovariantsofamultidrugresistantmycobacteriumtuberculosisstrain AT bigifabiana singlenucleotidepolymorphismsmayexplainthecontrastingphenotypesoftwovariantsofamultidrugresistantmycobacteriumtuberculosisstrain AT soriamarceloabel singlenucleotidepolymorphismsmayexplainthecontrastingphenotypesoftwovariantsofamultidrugresistantmycobacteriumtuberculosisstrain
_version_	1768545160353808384

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

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