A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole

Detalhes bibliográficos
Autor(a) principal: Zingales, Bianca
Data de Publicação: 2015
Outros Autores: 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
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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spelling 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
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Fundação Oswaldo Cruz
publisher.none.fl_str_mv Fundação Oswaldo Cruz
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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