1. Molecular and biological characterization of a highly pathogenic Trypanosoma cruzi strain isolated from a patient with congenital infection.
- Author
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Gulin JEN, Bisio M, Rocco DM, Altcheh J, Solana ME, and García-Bournissen F
- Subjects
- Animals, Brain parasitology, Brain pathology, Chagas Disease drug therapy, Chagas Disease parasitology, Chagas Disease transmission, Chlorocebus aethiops, DNA, Protozoan analysis, Disease Models, Animal, Female, Heart parasitology, Humans, Infant, Infectious Disease Transmission, Vertical, Inhibitory Concentration 50, Male, Mice, Mice, Inbred BALB C, Muscle, Skeletal parasitology, Muscle, Skeletal pathology, Myocardium pathology, Nifurtimox pharmacology, Nitroimidazoles pharmacology, Parasitemia drug therapy, Parasitemia parasitology, Random Allocation, Trypanocidal Agents pharmacology, Trypanosoma cruzi classification, Trypanosoma cruzi drug effects, Trypanosoma cruzi genetics, Vero Cells, Chagas Disease congenital, Nifurtimox therapeutic use, Nitroimidazoles therapeutic use, Trypanocidal Agents therapeutic use, Trypanosoma cruzi pathogenicity
- Abstract
Although many Trypanosoma cruzi (T. cruzi) strains isolated from a wide range of hosts have been characterized, there is a lack of information about biological features from vertically transmitted strains. We describe the molecular and biological characteristics of the T. cruzi VD strain isolated from a congenital Chagas disease patient. The VD strain was typified as DTU TcVI; in vitro sensitivity to nifurtimox (NFX) and beznidazole (BZ) were 2.88 μM and 6.19 μM respectively, while inhibitory concentrations for intracellular amastigotes were 0.24 μM for BZ, and 0.66 μM for NFX. Biological behavior of VD strain was studied in a mouse model of acute infection, resulting in high levels of parasitemia and mortality with a rapid clearence of bloodstream trypomastigotes when treated with BZ or NFX, preventing mortality and reducing parasitic load and intensity of inflammatory infiltrate in skeletal and cardiac muscle. Treatment-induced parasitological cure, evaluated after immunossupression were 41% and 35% for BZ and NFX treatment respectively, suggesting a partial response to these drugs in elimination of parasite burden. This exhaustive characterization of this T. cruzi strain provides the basis for inclusion of this strain in a panel of reference strains for drug screening and adds a new valuable tool for the study of experimental T. cruzi infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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