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A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance

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dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Requena, David
dc.contributor.author Gushiken, Eduardo
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Antiparra, Ricardo
dc.contributor.author Lucero, Bryan
dc.contributor.author Lizárraga, Pilar
dc.contributor.author Cieza, Basilio
dc.contributor.author Roncal, Elisa
dc.contributor.author Grandjean, Louis
dc.contributor.author Pain, Arnab
dc.contributor.author McNerney, Ruth
dc.contributor.author Clark, Taane G.
dc.contributor.author Moore, David Alexander James
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.date.accessioned 2019-01-25T15:02:14Z
dc.date.available 2019-01-25T15:02:14Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4586
dc.description.abstract BACKGROUND: Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear. RESULTS: We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion. CONCLUSIONS: These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets. en_US
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartofseries BMC Genomics
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Genomics en_US
dc.subject Mutation en_US
dc.subject Antitubercular Agents/pharmacology en_US
dc.subject Drug Resistance, Bacterial/genetics en_US
dc.subject Drugs en_US
dc.subject Efflux pump en_US
dc.subject Genes en_US
dc.subject Genes, Bacterial/genetics en_US
dc.subject Genome en_US
dc.subject Genotype en_US
dc.subject MDR en_US
dc.subject Metallochaperone en_US
dc.subject Mutations en_US
dc.subject Mycobacterium tuberculosis/drug effects/genetics en_US
dc.subject Phylogeny en_US
dc.subject Polymorphism, Single Nucleotide en_US
dc.subject Pyrazinamide en_US
dc.subject Pyrazinamide/pharmacology en_US
dc.subject Resistance en_US
dc.subject Tuberculosis en_US
dc.title A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1186/s12864-017-4146-z
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.07
dc.relation.issn 1471-2164


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