A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole
Mem. Inst. Oswaldo Cruz
;
110(3): 433-444, 05/2015. tab, graf
Article
in English
| LILACS
| ID: lil-745976
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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Trypanocidal Agents
/
Trypanosoma cruzi
/
Drug Resistance
/
ATP-Binding Cassette Transporters
/
Nitroimidazoles
Limits:
Animals
/
Humans
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2015
Type:
Article
/
Project document
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade de São Paulo/BR
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