A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/12234 |
Resumo: | Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil. |
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Zingales, BiancaAraujo, Rafael Gomes AquinoFranco, JaquesAguiar, Pedro Henrique NascimentoNunes, Solange LessaSilva, Marcelo NunesIenne, SusanMachado, Carlos RenatoBrandão, AdeiltonMoreno, Margoth2015-11-16T12:12:42Z2015-11-16T12:12:42Z2015ZINGALES, Bianca; et al. A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole. Mem Inst Oswaldo Cruz, v.110, n.3, p. 433-444, May 2015.0074-0276https://www.arca.fiocruz.br/handle/icict/1223410.1590/0074-027601404071678-8060engFundação Oswaldo CruzA novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazoleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departtamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departtamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil.Benznidazole (BZ) is one of the two drugs used for Chagas disease treatment. Nevertheless therapeutic failures of BZ have been reported, which were mostly attributed to variable drug susceptibility among Trypanosoma cruzi strains. ATP-binding cassette (ABC) transporters are involved in a variety of translocation processes and some members have been implicated in drug resistance. Here we report the characterisation of the first T. cruzi ABCG transporter gene, named TcABCG1, which is over-expressed in parasite strains naturally resistant to BZ. Comparison of TcABCG1 gene sequence of two TcI BZ-resistant strains with CL Brener BZ-susceptible strain showed several single nucleotide polymorphisms, which determined 11 amino acid changes. CL Brener transfected with TcI transporter genes showed 40-47% increased resistance to BZ, whereas no statistical significant increment in drug resistance was observed when CL Brener was transfected with the homologous gene. Only in the parasites transfected with TcI genes there was 2-2.6-fold increased abundance of TcABCG1 transporter protein. The analysis in wild type strains also suggests that the level of TcABCG1 transporter is related to BZ natural resistance. The characteristics of untranslated regions of TcABCG1 genes of BZ-susceptible and resistant strains were investigated by computational tools.Chagas diseaseBenznidazole resistanceABCG transporterT. cruzi strainsTranscript abundanceSingle nucleotide polymorphismsDoença de ChagasTrypanosoma cruziinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12234/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALadeilton_brandão_etal_IOC_2015.pdfadeilton_brandão_etal_IOC_2015.pdfapplication/pdf1406867https://www.arca.fiocruz.br/bitstream/icict/12234/2/adeilton_brand%c3%a3o_etal_IOC_2015.pdfaf27900f8f05d46d7ea10200cbff5311MD52TEXTadeilton_brandão_etal_IOC_2015.pdf.txtadeilton_brandão_etal_IOC_2015.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole |
title |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole |
spellingShingle |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole Zingales, Bianca Chagas disease Benznidazole resistance ABCG transporter T. cruzi strains Transcript abundance Single nucleotide polymorphisms Doença de Chagas Trypanosoma cruzi |
title_short |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole |
title_full |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole |
title_fullStr |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole |
title_full_unstemmed |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole |
title_sort |
A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole |
author |
Zingales, Bianca |
author_facet |
Zingales, Bianca Araujo, Rafael Gomes Aquino Franco, Jaques Aguiar, Pedro Henrique Nascimento Nunes, Solange Lessa Silva, Marcelo Nunes Ienne, Susan Machado, Carlos Renato Brandão, Adeilton Moreno, Margoth |
author_role |
author |
author2 |
Araujo, Rafael Gomes Aquino Franco, Jaques Aguiar, Pedro Henrique Nascimento Nunes, Solange Lessa Silva, Marcelo Nunes Ienne, Susan Machado, Carlos Renato Brandão, Adeilton Moreno, Margoth |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Zingales, Bianca Araujo, Rafael Gomes Aquino Franco, Jaques Aguiar, Pedro Henrique Nascimento Nunes, Solange Lessa Silva, Marcelo Nunes Ienne, Susan Machado, Carlos Renato Brandão, Adeilton Moreno, Margoth |
dc.subject.en.pt_BR.fl_str_mv |
Chagas disease Benznidazole resistance ABCG transporter T. cruzi strains Transcript abundance Single nucleotide polymorphisms |
topic |
Chagas disease Benznidazole resistance ABCG transporter T. cruzi strains Transcript abundance Single nucleotide polymorphisms Doença de Chagas Trypanosoma cruzi |
dc.subject.decs.pt_BR.fl_str_mv |
Doença de Chagas Trypanosoma cruzi |
description |
Universidade de São Paulo. Instituto de Química. Departamento de Bioquímica. São Paulo, SP, Brasil. |
publishDate |
2015 |
dc.date.accessioned.fl_str_mv |
2015-11-16T12:12:42Z |
dc.date.available.fl_str_mv |
2015-11-16T12:12:42Z |
dc.date.issued.fl_str_mv |
2015 |
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.citation.fl_str_mv |
ZINGALES, Bianca; et al. A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole. Mem Inst Oswaldo Cruz, v.110, n.3, p. 433-444, May 2015. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/12234 |
dc.identifier.issn.none.fl_str_mv |
0074-0276 |
dc.identifier.doi.none.fl_str_mv |
10.1590/0074-02760140407 |
dc.identifier.eissn.none.fl_str_mv |
1678-8060 |
identifier_str_mv |
ZINGALES, Bianca; et al. A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole. Mem Inst Oswaldo Cruz, v.110, n.3, p. 433-444, May 2015. 0074-0276 10.1590/0074-02760140407 1678-8060 |
url |
https://www.arca.fiocruz.br/handle/icict/12234 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Fundação Oswaldo Cruz |
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Fundação Oswaldo Cruz |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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