Título:	Trypanosoma cruzi kDNA minicircle sequences integration into the vertebrate host genome : a biomarker for monitoring the efficacy of multidrug treatment of Chagas disease
Autor(es):	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
Afiliação do autor:	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
Assunto:	Trypanosoma cruzi Transferência de kDNA Biomarcadores Tratamento com múltiplas drogas Chagas, Doença de
Data de publicação:	2023
Editora:	Orion Journals
Referência:	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.
Abstract:	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.
Unidade Acadêmica:	Faculdade de Medicina (FMD)
Licença:	Copyright © 2023 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0.
DOI:	https://doi.org/10.53430/ijsru.2023.5.1.0026
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