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...
- 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)
id |
EDOCUR2_62a27eef65d8da3a831faf3436a183d4 |
---|---|
oai_identifier_str |
oai:repository.urosario.edu.co:10336/22522 |
network_acronym_str |
EDOCUR2 |
network_name_str |
Repositorio EdocUR - U. Rosario |
repository_id_str |
|
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 |
dc.relation.uri.spa.fl_str_mv |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-33746899375&doi=10.1128%2fAAC.00112-06&partnerID=40&md5=eaf1a6964eb4ebde478da6880ba6f4d8 |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
rights_invalid_str_mv |
Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
institution |
Universidad del Rosario |
dc.source.instname.spa.fl_str_mv |
instname:Universidad del Rosario |
dc.source.reponame.spa.fl_str_mv |
reponame:Repositorio Institucional EdocUR |
bitstream.url.fl_str_mv |
https://repository.urosario.edu.co/bitstreams/b40a2507-d071-4643-8590-e6fd014791cd/download https://repository.urosario.edu.co/bitstreams/4cda88a1-a430-4e88-9b56-fde6f17aef97/download https://repository.urosario.edu.co/bitstreams/2f6d63f1-54f7-4434-9293-4a15b31bfe75/download |
bitstream.checksum.fl_str_mv |
97b76d0713c80a0d5652f2af21e3a0ae 6d65923b3eef6a5bf6d829d310aae917 b47eb1f720613642d84be09e189c750f |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio institucional EdocUR |
repository.mail.fl_str_mv |
edocur@urosario.edu.co |
_version_ |
1814167735084515328 |
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 |