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Master's Dissertation
DOI
10.11606/D.42.2014.tde-13082014-185755
Document
Author
Full name
Jaques Franco de Carvalho Junior
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Zingales, Bianca Silvana (President)
Muñiz, Bruno Dallagiovanna
Sabbaga, Maria Carolina Quartim Barbosa Elias
Title in Portuguese
O transportador ABC de Trypanosoma cruzi TcABCG1 potencialmente envolvido na resistência a benznidazol: características e filogenia.
Keywords in Portuguese
Cepas de Trypanosoma cruzi
Filogenia
Resistência a benznidazol
Transportador ABC
Abstract in Portuguese
Benznidazol (BZ), fármaco utilizado para o tratamento da doença de Chagas, apresenta eficácia limitada na fase crônica da doença. Falhas terapêuticas foram atribuídas majoritariamente a diferenças na suscetibilidade a BZ entre as cepas do T. cruzi. Resultados prévios de nosso grupo indicam que o gene de um transportador ABC da subfamília G, TcABCG1, encontra-se super-expresso em cepas resistentes a BZ. Transportadores ABCG foram associados a resistência a drogas em vários organismos. O objetivo central do presente estudo foi caracterizar o gene TcABCG1 em cepas de diferentes linhagens e cuja suscetibilidade a BZ foi definida. A sequência do gene TcABCG1 (1.998 pb) de 14 cepas foi determinada. Observamos algumas variações de aminoácidos na proteína ABC entre as cepas. Análises genealógicas de TcABCG1 definiram quatro clados (TcI, TcII, TcIII e Tcbat). Os dois haplótipos das cepas híbridas TcV e TcVI agruparam com os clados TcII e TcIII. Dados de imunofluorescência indireta em epimastigotas indicam que TcABCG1 está localizado em vesículas intracelulares.
Title in English
The ABC transporter of Trypanosoma cruzi TcABCG1 potentially involved in benznidazole resistance: characteristics and phylogeny.
Keywords in English
Trypanosoma cruzi strains
ABC transporter
Benznidazole resistance
Phylogeny
Abstract in English
Benznidazole (BZ), drug employed for Chagas disease treatment, has limited efficacy in the chronic phase of the disease. Treatment failures have been attributed mostly to differences in BZ susceptibility among T. cruzi strains. Previous data from our group indicate that one ABC transporter gene of the G subfamily, named TcABCG1, is overexpressed in BZ-resistant strains. ABCG transporters have been associated to drug resistance in several organisms. The central goal of the present study was to characterize TcABCG1 gene in strains belonging to different lineages and of defined BZ susceptibility. TcABCG1 gene sequence (1,998 bp) of 14 strains was determined. Few amino acid substitutions were detected in the ABC transporter protein among the strains. Genealogic analyses of TcABCG1 showed four distinct clades (TcI, TcII, TcIII and Tcbat). The two haplotypes of TcV and TcVI hybrid strains clustered with TcII and TcIII clades. Indirect immunofluorescence analysis in epimastigote forms indicated that TcABCG1 is localized to intracellular vesicles.
 
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Publishing Date
2014-08-14
 
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