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Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis

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dc.creatorHazbón M.H.spa
dc.creatorBrimacombe M.spa
dc.creatorDel Valle M.B.spa
dc.creatorCavatore M.spa
dc.creatorGuerrero M.I.spa
dc.creatorVarma-Basil M.spa
dc.creatorBillman-Jacobe H.spa
dc.creatorLavender C.spa
dc.creatorFyfe J.spa
dc.creatorGarcía-García L.spa
dc.creatorLeón C.I.spa
dc.creatorBose M.spa
dc.creatorChaves F.spa
dc.creatorMurray M.spa
dc.creatorEisenach K.D.spa
dc.creatorSifuentes-Osornio J.spa
dc.creatorCave M.D.spa
dc.creatorDe León A.P.spa
dc.creatorAlland D.spa
dc.date.accessioned2020-05-25T23:56:47Z
dc.date.available2020-05-25T23:56:47Z
dc.date.created2006spa
dc.description.abstractThe molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG3l5 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes. Copyright © 2006, American Society for Microbiology. All Rights Reserved.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1128/AAC.00112-06
dc.identifier.issn10986596
dc.identifier.issn00664804
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22522
dc.language.isoengspa
dc.relation.citationEndPage2649
dc.relation.citationIssueNo. 8
dc.relation.citationStartPage2640
dc.relation.citationTitleAntimicrobial Agents and Chemotherapy
dc.relation.citationVolumeVol. 50
dc.relation.ispartofAntimicrobial Agents and Chemotherapy, ISSN:10986596, 00664804, Vol.50, No.8 (2006); pp. 2640-2649spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-33746899375&doi=10.1128%2fAAC.00112-06&partnerID=40&md5=eaf1a6964eb4ebde478da6880ba6f4d8spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordDnaspa
dc.subject.keywordintergeniceng
dc.subject.keywordIsoniazidspa
dc.subject.keywordAhpc genespa
dc.subject.keywordAllelespa
dc.subject.keywordArticlespa
dc.subject.keywordGenespa
dc.subject.keywordGene identificationspa
dc.subject.keywordGene interactionspa
dc.subject.keywordGene mutationspa
dc.subject.keywordHumanspa
dc.subject.keywordInha genespa
dc.subject.keywordKasa genespa
dc.subject.keywordKatg genespa
dc.subject.keywordMolecular geneticsspa
dc.subject.keywordMultidrug resistancespa
dc.subject.keywordMycobacterium tuberculosisspa
dc.subject.keywordNdh genespa
dc.subject.keywordNonhumanspa
dc.subject.keywordNucleotide sequencespa
dc.subject.keywordPhenotypespa
dc.subject.keywordPopulation geneticsspa
dc.subject.keywordPriority journalspa
dc.subject.keywordPromoter regionspa
dc.subject.keywordStatistical analysisspa
dc.subject.keywordStrain differencespa
dc.subject.keywordAllelesspa
dc.subject.keywordAntibioticseng
dc.subject.keywordAntitubercular agentsspa
dc.subject.keywordDna mutational analysisspa
dc.subject.keywordDnaeng
dc.subject.keywordDnaeng
dc.subject.keywordEthambutolspa
dc.subject.keywordEvolutionspa
dc.subject.keywordGene deletionspa
dc.subject.keywordGeneseng
dc.subject.keywordHumansspa
dc.subject.keywordIsoniazidspa
dc.subject.keywordMicrobial sensitivity testsspa
dc.subject.keywordMutationspa
dc.subject.keywordMycobacterium tuberculosisspa
dc.subject.keywordOpen reading framesspa
dc.subject.keywordPolymorphismeng
dc.subject.keywordPromoter regions (genetics)spa
dc.subject.keywordRifampinspa
dc.subject.keywordSequence analysiseng
dc.subject.keywordStreptomycinspa
dc.subject.keywordTuberculosiseng
dc.titlePopulation genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosisspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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