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Molecular characterization of susceptible and naturally resistant strains of Trypanosoma cruzi to benznidazole and nifurtimox

Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resistant to the nitroderivatives benznidazole and nifurtimox, were analyzed using the following molecular markers: (i) isoenzyme patterns of six enzymes; (ii) genetic variability assayed by randomly amplified polymorphic DNA (RAPD) wi...

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Published in:Molecular and biochemical parasitology 1998-06, Vol.93 (2), p.203-214
Main Authors: Murta, Silvane M.F, Gazzinelli, Ricardo T, Brener, Zigman, Romanha, Alvaro J
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description Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resistant to the nitroderivatives benznidazole and nifurtimox, were analyzed using the following molecular markers: (i) isoenzyme patterns of six enzymes; (ii) genetic variability assayed by randomly amplified polymorphic DNA (RAPD) with two different primers; and (iii) gene probes for P-glycoprotein (TcPGP), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the ribosomal RNA gene ( rDNA) and the mini-exon gene ( MEX). RAPD and isoenzyme profiles divided the T. cruzi strains into three groups, whereas the gene probes divided the T. cruzi strains in two groups. Strains classified as group I or II by RAPD or zymodemes Z1 or Z2 by isoenzyme analysis were either susceptible or naturally resistant to the nitroderivatives. In contrast, strains classified as group III by RAPD and zymodeme ZB by isoenzyme analysis were only drug susceptible and showed polymorphisms for HGPRT and TcPGP. No correlation was observed between drug susceptibility and polymorphisms of rDNA and MEX. Eighteen T. cruzi strains isolated from different geographic regions were included in this study. Thus, from a total of 45 T. cruzi strains analyzed, all 19 of zymodeme B were susceptible to the experimental treatment independent of their geographic origin.
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subjects Animals
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
benznidazole
Brazil
Chagas Disease - parasitology
Chemotherapy
DNA, Protozoan - genetics
DNA, Ribosomal - genetics
Drug Resistance
Exons - genetics
Genes, Protozoan
Genetic Variation
Glucose-6-Phosphate Isomerase - analysis
Humans
Hypoxanthine Phosphoribosyltransferase - genetics
hypoxanthine-guanine phosphoribosyltransferase
Isoenzymes - analysis
MEX protein
nifurtimox
Nifurtimox - pharmacology
Nitroimidazoles - pharmacology
Polymorphism, Genetic
Random Amplified Polymorphic DNA Technique
Randomly amplified polymorphic DNA
Trypanocidal Agents - pharmacology
Trypanosoma cruzi
Trypanosoma cruzi - classification
Trypanosoma cruzi - drug effects
Trypanosoma cruzi - enzymology
Trypanosoma cruzi - genetics
Zymodeme
zymodeme B
title Molecular characterization of susceptible and naturally resistant strains of Trypanosoma cruzi to benznidazole and nifurtimox
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