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

The 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 stati...

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Autores:
Tipo de recurso:
Fecha de publicación:
2006
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22522
Acceso en línea:
https://doi.org/10.1128/AAC.00112-06
https://repository.urosario.edu.co/handle/10336/22522
Palabra clave:
Dna
Ethambutol
Isoniazid
Ahpc gene
Allele
Article
Gene
Gene identification
Gene interaction
Gene mutation
Human
Inha gene
Kasa gene
Katg gene
Molecular genetics
Multidrug resistance
Mycobacterium tuberculosis
Ndh gene
Nonhuman
Nucleotide sequence
Phenotype
Population genetics
Priority journal
Promoter region
Statistical analysis
Strain difference
Alleles
Antitubercular agents
Dna mutational analysis
Ethambutol
Evolution
Gene deletion
Humans
Isoniazid
Microbial sensitivity tests
Mutation
Mycobacterium tuberculosis
Open reading frames
Promoter regions (genetics)
Rifampin
Streptomycin
intergenic
multidrug-resistant
dna
bacterial
bacterial
antitubercular
single nucleotide
Antibiotics
Dna
Dna
Genes
Polymorphism
Sequence analysis
Tuberculosis
Rights
License
Abierto (Texto Completo)
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dc.title.spa.fl_str_mv Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
title Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
spellingShingle Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
Dna
Ethambutol
Isoniazid
Ahpc gene
Allele
Article
Gene
Gene identification
Gene interaction
Gene mutation
Human
Inha gene
Kasa gene
Katg gene
Molecular genetics
Multidrug resistance
Mycobacterium tuberculosis
Ndh gene
Nonhuman
Nucleotide sequence
Phenotype
Population genetics
Priority journal
Promoter region
Statistical analysis
Strain difference
Alleles
Antitubercular agents
Dna mutational analysis
Ethambutol
Evolution
Gene deletion
Humans
Isoniazid
Microbial sensitivity tests
Mutation
Mycobacterium tuberculosis
Open reading frames
Promoter regions (genetics)
Rifampin
Streptomycin
intergenic
multidrug-resistant
dna
bacterial
bacterial
antitubercular
single nucleotide
Antibiotics
Dna
Dna
Genes
Polymorphism
Sequence analysis
Tuberculosis
title_short Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
title_full Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
title_fullStr Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
title_full_unstemmed Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
title_sort Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis
dc.subject.keyword.spa.fl_str_mv Dna
Ethambutol
Isoniazid
Ahpc gene
Allele
Article
Gene
Gene identification
Gene interaction
Gene mutation
Human
Inha gene
Kasa gene
Katg gene
Molecular genetics
Multidrug resistance
Mycobacterium tuberculosis
Ndh gene
Nonhuman
Nucleotide sequence
Phenotype
Population genetics
Priority journal
Promoter region
Statistical analysis
Strain difference
Alleles
Antitubercular agents
Dna mutational analysis
Ethambutol
Evolution
Gene deletion
Humans
Isoniazid
Microbial sensitivity tests
Mutation
Mycobacterium tuberculosis
Open reading frames
Promoter regions (genetics)
Rifampin
Streptomycin
topic Dna
Ethambutol
Isoniazid
Ahpc gene
Allele
Article
Gene
Gene identification
Gene interaction
Gene mutation
Human
Inha gene
Kasa gene
Katg gene
Molecular genetics
Multidrug resistance
Mycobacterium tuberculosis
Ndh gene
Nonhuman
Nucleotide sequence
Phenotype
Population genetics
Priority journal
Promoter region
Statistical analysis
Strain difference
Alleles
Antitubercular agents
Dna mutational analysis
Ethambutol
Evolution
Gene deletion
Humans
Isoniazid
Microbial sensitivity tests
Mutation
Mycobacterium tuberculosis
Open reading frames
Promoter regions (genetics)
Rifampin
Streptomycin
intergenic
multidrug-resistant
dna
bacterial
bacterial
antitubercular
single nucleotide
Antibiotics
Dna
Dna
Genes
Polymorphism
Sequence analysis
Tuberculosis
dc.subject.keyword.eng.fl_str_mv intergenic
multidrug-resistant
dna
bacterial
bacterial
antitubercular
single nucleotide
Antibiotics
Dna
Dna
Genes
Polymorphism
Sequence analysis
Tuberculosis
description The 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.
publishDate 2006
dc.date.created.spa.fl_str_mv 2006
dc.date.accessioned.none.fl_str_mv 2020-05-25T23:56:47Z
dc.date.available.none.fl_str_mv 2020-05-25T23:56:47Z
dc.type.eng.fl_str_mv article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.spa.spa.fl_str_mv Artículo
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1128/AAC.00112-06
dc.identifier.issn.none.fl_str_mv 10986596
00664804
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/22522
url https://doi.org/10.1128/AAC.00112-06
https://repository.urosario.edu.co/handle/10336/22522
identifier_str_mv 10986596
00664804
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.citationEndPage.none.fl_str_mv 2649
dc.relation.citationIssue.none.fl_str_mv No. 8
dc.relation.citationStartPage.none.fl_str_mv 2640
dc.relation.citationTitle.none.fl_str_mv Antimicrobial Agents and Chemotherapy
dc.relation.citationVolume.none.fl_str_mv Vol. 50
dc.relation.ispartof.spa.fl_str_mv Antimicrobial Agents and Chemotherapy, ISSN:10986596, 00664804, Vol.50, No.8 (2006); pp. 2640-2649
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spelling a057c776-131c-4312-ae93-eee2ae93c195-16271fdc0-e5af-466d-b341-d0a3acfa31b8-128f8cac0-c2f0-49f7-8b07-341667f050bc-1b3894893-776c-4eaf-8c8b-32326392790e-11e037fde-67ee-4f02-bbf4-dc7b999fa14b-1738c0a3e-2360-4aa6-a075-96174744d588-141e600a9-f33d-4fe9-b2d6-a7dd226d25b2-1270d8f08-61c6-486c-80c5-9c6a17aada62-1f6e9520d-bd3a-431b-8614-e1f7d7656d03-10b0da5e4-4e90-4161-a0b5-308501d5a499-18c411acc-892b-4dcd-9822-6abd925ec6a4-1f27cb281-318d-4bb4-a351-8ec1028a4f15-1414d3dcb-8654-4e10-9842-edba563803e7-1189a9112-421f-478d-94a1-9e16325cecfb-10656899d-a115-42e4-83aa-b524b65d782a-10b0aa8ba-b1cc-4707-8745-eea97a9cf883-1f672471e-5150-438a-99ac-eba9ecdf05b5-14264f668-39cc-4ac8-b5e8-f327e2cf7444-17473cf82-d97a-4130-a4ec-8feaceb42ba0-12020-05-25T23:56:47Z2020-05-25T23:56:47Z2006The 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.application/pdfhttps://doi.org/10.1128/AAC.00112-061098659600664804https://repository.urosario.edu.co/handle/10336/22522eng2649No. 82640Antimicrobial Agents and ChemotherapyVol. 50Antimicrobial Agents and Chemotherapy, ISSN:10986596, 00664804, Vol.50, No.8 (2006); pp. 2640-2649https://www.scopus.com/inward/record.uri?eid=2-s2.0-33746899375&doi=10.1128%2fAAC.00112-06&partnerID=40&md5=eaf1a6964eb4ebde478da6880ba6f4d8Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURDnaEthambutolIsoniazidAhpc geneAlleleArticleGeneGene identificationGene interactionGene mutationHumanInha geneKasa geneKatg geneMolecular geneticsMultidrug resistanceMycobacterium tuberculosisNdh geneNonhumanNucleotide sequencePhenotypePopulation geneticsPriority journalPromoter regionStatistical analysisStrain differenceAllelesAntitubercular agentsDna mutational analysisEthambutolEvolutionGene deletionHumansIsoniazidMicrobial sensitivity testsMutationMycobacterium tuberculosisOpen reading framesPromoter regions (genetics)RifampinStreptomycinintergenicmultidrug-resistantdnabacterialbacterialantitubercularsingle nucleotideAntibioticsDnaDnaGenesPolymorphismSequence analysisTuberculosisPopulation genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosisarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Hazbón M.H.Brimacombe M.Del Valle M.B.Cavatore M.Guerrero M.I.Varma-Basil M.Billman-Jacobe H.Lavender C.Fyfe J.García-García L.León C.I.Bose M.Chaves F.Murray M.Eisenach K.D.Sifuentes-Osornio J.Cave M.D.De León A.P.Alland D.ORIGINALAntimicrobial-Agents-and-Chemotherapy-2006-Hazbon-2640-full.pdfapplication/pdf386596https://repository.urosario.edu.co/bitstreams/b40a2507-d071-4643-8590-e6fd014791cd/download97b76d0713c80a0d5652f2af21e3a0aeMD51TEXTAntimicrobial-Agents-and-Chemotherapy-2006-Hazbon-2640-full.pdf.txtAntimicrobial-Agents-and-Chemotherapy-2006-Hazbon-2640-full.pdf.txtExtracted texttext/plain63902https://repository.urosario.edu.co/bitstreams/4cda88a1-a430-4e88-9b56-fde6f17aef97/download6d65923b3eef6a5bf6d829d310aae917MD52THUMBNAILAntimicrobial-Agents-and-Chemotherapy-2006-Hazbon-2640-full.pdf.jpgAntimicrobial-Agents-and-Chemotherapy-2006-Hazbon-2640-full.pdf.jpgGenerated Thumbnailimage/jpeg5000https://repository.urosario.edu.co/bitstreams/2f6d63f1-54f7-4434-9293-4a15b31bfe75/downloadb47eb1f720613642d84be09e189c750fMD5310336/22522oai:repository.urosario.edu.co:10336/225222022-05-02 07:37:14.226849https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co