Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/12234
Title: A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole
Authors: 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
Affilliation: 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.
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.
Abstract: 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.
Keywords: Chagas disease
Benznidazole resistance
ABCG transporter
T. cruzi strains
Transcript abundance
Single nucleotide polymorphisms
DeCS: Doença de Chagas
Trypanosoma cruzi
Issue Date: 2015
Publisher: Fundação Oswaldo Cruz
Citation: 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.
DOI: 10.1590/0074-02760140407
ISSN: 0074-0276
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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