Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease

Detalhes bibliográficos
Autor(a) principal: Teixeira, Antonio Raimundo Lima Cruz
Data de Publicação: 2023
Outros Autores: Gomes, Clever Cardoso, Sá, Adriana Alves, Nascimento, Rubens José, Lauria-Pires, Liana, Castro, Ana Maria, Bernal, Francisco Ernesto Moreno, Sousa, Alessandro Oliveira de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UnB
Texto Completo: http://repositorio2.unb.br/jspui/handle/10482/46019
https://doi.org/10.53430/ijsru.2023.5.1.0026
Resumo: The protist Trypanosoma cruzi inserts kinetoplast DNA minicircle sequences into the host genome. Sensitive PCR with specific primer sets revealed protozoan nuclear DNA and kinetoplast DNA in agarose gels bands probed with radiolabel specific sequences for tissues of T. cruzi-infected rabbits and mice. Avian species are refractory to the infection, but chicks that hatched from T. cruzi-inoculated eggs retained the kinetoplast DNA in the embryonic germ line cells and developed parasite-free Chagas disease-like cardiomyopathy. A Target-primer TAIL-PCR with specific primer sets, Southern hybridization, cloning, and sequencing of the amplification products revealed kinetoplast minicircle sequences integration sites mainly in LINE-1 transposable elements and hitchhiking to several loci. This kinetoplast DNA biomarker was used to monitor the effect of multidrug treatment of T. cruzi-infected mice. A trypanocidal nitro heterocyclic compound in combination with an array of inhibitors of eukaryotic cell division prevented minicircle sequences transfer. Nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of T. cruzi-infected mice with benznidazole, azidothymidine and ofloxacin lowered the rate of minicircle sequences integrations into the mouse genome by 2.44-fold and reduced the rejection of the target heart cells.
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spelling Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas diseaseTrypanosoma cruziTransferência de kDNABiomarcadorTratamento com múltiplas drogasChagas, Doença deThe protist Trypanosoma cruzi inserts kinetoplast DNA minicircle sequences into the host genome. Sensitive PCR with specific primer sets revealed protozoan nuclear DNA and kinetoplast DNA in agarose gels bands probed with radiolabel specific sequences for tissues of T. cruzi-infected rabbits and mice. Avian species are refractory to the infection, but chicks that hatched from T. cruzi-inoculated eggs retained the kinetoplast DNA in the embryonic germ line cells and developed parasite-free Chagas disease-like cardiomyopathy. A Target-primer TAIL-PCR with specific primer sets, Southern hybridization, cloning, and sequencing of the amplification products revealed kinetoplast minicircle sequences integration sites mainly in LINE-1 transposable elements and hitchhiking to several loci. This kinetoplast DNA biomarker was used to monitor the effect of multidrug treatment of T. cruzi-infected mice. A trypanocidal nitro heterocyclic compound in combination with an array of inhibitors of eukaryotic cell division prevented minicircle sequences transfer. Nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of T. cruzi-infected mice with benznidazole, azidothymidine and ofloxacin lowered the rate of minicircle sequences integrations into the mouse genome by 2.44-fold and reduced the rejection of the target heart cells.Faculdade de Medicina (FMD)Orion JournalsUniversity of Brasília, Faculty of Medicine, Department of PathologyFederal University of Goiás, Department of Histology, Embryology and Cell BiologyUniversity of Brasília, Faculty of Medicine, Department of PathologySambaia Regional HospitalUniversity of Brasília, Faculty of Medicine, Department of PathologyMinistry of Science and Technology, National Technical Commission on BiosafetyUniversity of Brasília, Faculty of Medicine, Department of PathologyCatholic University of Brasilia, Department of MedicineFederal University of Goiás, Institute for Tropical Pathology and Public HealthUniversity of Brasília, Faculty of Agronomy and Veterinary Medicine, Animal Welfare and Avian Pathology LaboratoryUniversity of Brasília, Faculty of Medicine, Department of PathologyLogistic Office for Health, Federal District Health DepartmentTeixeira, Antonio Raimundo Lima CruzGomes, Clever CardosoSá, Adriana AlvesNascimento, Rubens JoséLauria-Pires, LianaCastro, Ana MariaBernal, Francisco Ernesto MorenoSousa, Alessandro Oliveira de2023-07-05T12:24:26Z2023-07-05T12:24:26Z2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfTEIXEIRA, Antonio Raimundo Lima et al. Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome: a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease. International Journal of Scientific Research Updates, S.l., v. 5, n. 1, 170-207, 2023. DOI: https://doi.org/10.53430/ijsru.2023.5.1.0026. Disponível em: https://orionjournals.com/ijsru/content/trypanosoma-cruzi-kdna-minicircle-sequences-integration-vertebrate-host-genome-biomarker. Acesso em: 05 julho 2023.http://repositorio2.unb.br/jspui/handle/10482/46019https://doi.org/10.53430/ijsru.2023.5.1.0026engCopyright © 2023 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UnBinstname:Universidade de Brasília (UnB)instacron:UNB2023-07-11T10:31:34Zoai:repositorio.unb.br:10482/46019Repositório InstitucionalPUBhttps://repositorio.unb.br/oai/requestrepositorio@unb.bropendoar:2023-07-11T10:31:34Repositório Institucional da UnB - Universidade de Brasília (UnB)false
dc.title.none.fl_str_mv Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
title Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
spellingShingle Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
Teixeira, Antonio Raimundo Lima Cruz
Trypanosoma cruzi
Transferência de kDNA
Biomarcador
Tratamento com múltiplas drogas
Chagas, Doença de
title_short Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
title_full Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
title_fullStr Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
title_full_unstemmed Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
title_sort Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
author Teixeira, Antonio Raimundo Lima Cruz
author_facet Teixeira, Antonio Raimundo Lima Cruz
Gomes, Clever Cardoso
Sá, Adriana Alves
Nascimento, Rubens José
Lauria-Pires, Liana
Castro, Ana Maria
Bernal, Francisco Ernesto Moreno
Sousa, Alessandro Oliveira de
author_role author
author2 Gomes, Clever Cardoso
Sá, Adriana Alves
Nascimento, Rubens José
Lauria-Pires, Liana
Castro, Ana Maria
Bernal, Francisco Ernesto Moreno
Sousa, Alessandro Oliveira de
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv University of Brasília, Faculty of Medicine, Department of Pathology
Federal University of Goiás, Department of Histology, Embryology and Cell Biology
University of Brasília, Faculty of Medicine, Department of Pathology
Sambaia Regional Hospital
University of Brasília, Faculty of Medicine, Department of Pathology
Ministry of Science and Technology, National Technical Commission on Biosafety
University of Brasília, Faculty of Medicine, Department of Pathology
Catholic University of Brasilia, Department of Medicine
Federal University of Goiás, Institute for Tropical Pathology and Public Health
University of Brasília, Faculty of Agronomy and Veterinary Medicine, Animal Welfare and Avian Pathology Laboratory
University of Brasília, Faculty of Medicine, Department of Pathology
Logistic Office for Health, Federal District Health Department
dc.contributor.author.fl_str_mv Teixeira, Antonio Raimundo Lima Cruz
Gomes, Clever Cardoso
Sá, Adriana Alves
Nascimento, Rubens José
Lauria-Pires, Liana
Castro, Ana Maria
Bernal, Francisco Ernesto Moreno
Sousa, Alessandro Oliveira de
dc.subject.por.fl_str_mv Trypanosoma cruzi
Transferência de kDNA
Biomarcador
Tratamento com múltiplas drogas
Chagas, Doença de
topic Trypanosoma cruzi
Transferência de kDNA
Biomarcador
Tratamento com múltiplas drogas
Chagas, Doença de
description The protist Trypanosoma cruzi inserts kinetoplast DNA minicircle sequences into the host genome. Sensitive PCR with specific primer sets revealed protozoan nuclear DNA and kinetoplast DNA in agarose gels bands probed with radiolabel specific sequences for tissues of T. cruzi-infected rabbits and mice. Avian species are refractory to the infection, but chicks that hatched from T. cruzi-inoculated eggs retained the kinetoplast DNA in the embryonic germ line cells and developed parasite-free Chagas disease-like cardiomyopathy. A Target-primer TAIL-PCR with specific primer sets, Southern hybridization, cloning, and sequencing of the amplification products revealed kinetoplast minicircle sequences integration sites mainly in LINE-1 transposable elements and hitchhiking to several loci. This kinetoplast DNA biomarker was used to monitor the effect of multidrug treatment of T. cruzi-infected mice. A trypanocidal nitro heterocyclic compound in combination with an array of inhibitors of eukaryotic cell division prevented minicircle sequences transfer. Nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of T. cruzi-infected mice with benznidazole, azidothymidine and ofloxacin lowered the rate of minicircle sequences integrations into the mouse genome by 2.44-fold and reduced the rejection of the target heart cells.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-05T12:24:26Z
2023-07-05T12:24:26Z
2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv TEIXEIRA, Antonio Raimundo Lima et al. Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome: a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease. International Journal of Scientific Research Updates, S.l., v. 5, n. 1, 170-207, 2023. DOI: https://doi.org/10.53430/ijsru.2023.5.1.0026. Disponível em: https://orionjournals.com/ijsru/content/trypanosoma-cruzi-kdna-minicircle-sequences-integration-vertebrate-host-genome-biomarker. Acesso em: 05 julho 2023.
http://repositorio2.unb.br/jspui/handle/10482/46019
https://doi.org/10.53430/ijsru.2023.5.1.0026
identifier_str_mv TEIXEIRA, Antonio Raimundo Lima et al. Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome: a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease. International Journal of Scientific Research Updates, S.l., v. 5, n. 1, 170-207, 2023. DOI: https://doi.org/10.53430/ijsru.2023.5.1.0026. Disponível em: https://orionjournals.com/ijsru/content/trypanosoma-cruzi-kdna-minicircle-sequences-integration-vertebrate-host-genome-biomarker. Acesso em: 05 julho 2023.
url http://repositorio2.unb.br/jspui/handle/10482/46019
https://doi.org/10.53430/ijsru.2023.5.1.0026
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Orion Journals
publisher.none.fl_str_mv Orion Journals
dc.source.none.fl_str_mv reponame:Repositório Institucional da UnB
instname:Universidade de Brasília (UnB)
instacron:UNB
instname_str Universidade de Brasília (UnB)
instacron_str UNB
institution UNB
reponame_str Repositório Institucional da UnB
collection Repositório Institucional da UnB
repository.name.fl_str_mv Repositório Institucional da UnB - Universidade de Brasília (UnB)
repository.mail.fl_str_mv repositorio@unb.br
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