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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.

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The kDNA minicircle size was analyzed in 15 species of choanomastigote-shaped trypanosomatids and four main groups of species were identified: (1) "Crithidia" deanei, "C." desouzai and "Herpetomonas" roitmani, which presented the largest molecules (> or = 3,800 bp), (2) "C." oncopelti with minicircles of at least four different sizes within 1,300-2,650 bp, (3) C. fasciculata, C. guilhermei and C. luciliae, having at least two sizes of minicircle (2,650 bp and 3,000 bp) and (4) a heterogeneous group of species presenting minicircles of a single size, including several Crithidia spp. (having 1,600 bp or 1,700 bp minicircles) and two Proteomonas spp. presenting the smallest minicircles (about 1,500 bp). These results were compared with other observations and discussed from a taxonomic point of view.