A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole
| Autor: | Marcelo Nunes da Silva, Solange Lessa Nunes, Rafael Gomes Aquino de Araújo, Bianca Zingales, Jaques Franco, Pedro Henrique Nascimento Aguiar, Carlos Renato Machado, Margoth Mitchela Vigo Moreno, Susan Ienne, Adeilton Brandão |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Microbiology (medical)
Chagas disease lcsh:Arctic medicine. Tropical medicine Genotype lcsh:RC955-962 Trypanosoma cruzi lcsh:QR1-502 Drug Resistance Drug resistance lcsh:Microbiology strains single nucleotide polymorphisms Parasitic Sensitivity Tests medicine Animals Humans Gene Phylogeny Genetics biology Membrane transport protein transcript abundance Wild type Membrane Transport Proteins Transporter Articles DNA Protozoan biology.organism_classification medicine.disease Trypanocidal Agents ABCG transporter T. cruzi Benznidazole Nitroimidazoles benznidazole resistance biology.protein ATP-Binding Cassette Transporters medicine.drug |
| Zdroj: | Memórias do Instituto Oswaldo Cruz, Volume: 110, Issue: 3, Pages: 433-444, Published: 28 APR 2015 Memórias do Instituto Oswaldo Cruz Memórias do Instituto Oswaldo Cruz., Vol 110, Iss 3, Pp 433-444 (2015) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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