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dc.contributor.authorSheen, Patricia
dc.contributor.authorRequena, David
dc.contributor.authorGushiken, Eduardo
dc.contributor.authorGilman, Robert H.
dc.contributor.authorAntiparra, Ricardo
dc.contributor.authorLucero, Bryan
dc.contributor.authorLizárraga, Pilar
dc.contributor.authorCieza, Basilio
dc.contributor.authorRoncal, Elisa
dc.contributor.authorGrandjean, Louis
dc.contributor.authorPain, Arnab
dc.contributor.authorMcNerney, Ruth
dc.contributor.authorClark, Taane G.
dc.contributor.authorMoore, David J.
dc.contributor.authorZimic, Mirko
dc.date.accessioned2017-10-17T11:47:39Z
dc.date.available2017-10-17T11:47:39Z
dc.date.issued2017-10-11
dc.identifier.citationSheen P, Requena D, Gushiken E, Gilman RH, Antiparra R, et al. (2017) A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance. BMC Genomics 18. Available: http://dx.doi.org/10.1186/s12864-017-4146-z.
dc.identifier.issn1471-2164
dc.identifier.pmid29020922
dc.identifier.doi10.1186/s12864-017-4146-z
dc.identifier.urihttp://hdl.handle.net/10754/625883
dc.description.abstractTuberculosis (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.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.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.
dc.description.sponsorshipSome of this research and some members of the research team were funded by the Wellcome Trust (award 099805/Z/12/Z); the charity IFHAD: Innovation For Health And Development; DFID-CSCF; the Joint Global Health Trials consortium (MRC, DFID & Wellcome Trust); the Imperial College Biomedical Research Centre; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health US, under the terms of Award 1R01TW008669-01. This study was also partially funded by Lóreal UNESCO, TWAS and Grand Challenge Canada. PS is a Wellcome Trust fellow. TGC receives funding from the MRC UK (MR/K000551/1, MR/M01360X/1, MR/N010469/1, MC_PC_15103). AP is supported by faculty baseline research fund from KAUST. MZ is a Bill and Melinda Gates Foundation grantee.
dc.publisherSpringer Nature
dc.relation.urlhttps://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-4146-z
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGenome
dc.subjectGenes
dc.subjectResistance
dc.subjectTuberculosis
dc.subjectDrugs
dc.subjectMDR
dc.subjectMutations
dc.subjectEfflux pump
dc.subjectPyrazinamide
dc.subjectmetallochaperone
dc.titleA multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.identifier.journalBMC Genomics
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionLaboratorio de Bioinformática y Biología Molecular. Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, 31, Lima, Peru.
dc.contributor.institutionDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Room 5515, Baltimore, MD, 21205, USA.
dc.contributor.institutionDepartment of Infection, Immunology and Rheumatology, Institute of Child Health, University College London, 30 Guilford St, London, WC1N 1EH, UK.
dc.contributor.institutionFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.
dc.contributor.institutionFaculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.
dc.contributor.institutionLaboratorio de Bioinformática y Biología Molecular. Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, 31, Lima, Peru. mirko.zimic@upch.pe.
kaust.personPain, Arnab
refterms.dateFOA2018-06-14T05:18:27Z


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This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Except where otherwise noted, this item's license is described as This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.