HETEROGENEIDAD EN CEPAS DE TRYPANOSOMA CRUZI DE TIPO DTU-Is
Chagas disease is an infection caused by the protozoan Trypanosoma cruzi being endemic in twenty one countries of Latin America and constitutes a mayor public health problem. It currently affects about 10 million individuals and up to 25% of the Latin America people are exposed to infection. During last years it was observed an increase in the prevalence of death per year. According to DNDi data (year 2009) Chagas disease “kills more people in the region than any other parasite-borne disease, including malaria”. In addition, the increasing number of migrants from Latin-American countries has globally spread the T. cruzi infection to non-endemic areas. Nowadays, other ways of infection such as congenital transmission, blood transfusion and organ transplantation are becoming prevalent and relevant from a public health point of view in both endemic and non-endemic countries. The clinical symptoms of Chagas disease are quite variable, -most of the patients are asymptomatic-, but they also can course with severe and chronic cardiovascular and/or gastrointestinal afflictions. The epidemiologic complexity and the great variety of the pathogenicity of T. cruzi are a consequence of host genetic factors and the high genetic variability and multiclonality of natural T. cruzi strains populations [1]. This genetic heterogeneity was recognized long ago studying the enzyme electrophoresis patterns [2] and so demonstrating the clonal propagation of T. cruzi isolates [3, 4].
Six Discrete Typing Units (DTU) were successfully identified by Multi-Locus Enzyme Electrophoresis (MLEE), Random Amplification of Polymorphic DNA (RAPD) and by the analysis of the polymorphism rRNA and mini-exon gene sequences [5]. These DTUs are actually named from TcI to TcVI [6]. TcI and TcII are considered the parental phylogenetic lineages while the other DTUs seem to be the product of successive hybridization events [7]. However, recently, based on the analysis of the polymorphism of the miniexon gene’s intergenic partial region four haplotypes have been identified in the DTU-TcI (TcIa-Id) [8].
Mouse models have been used to characterize T. cruzi strains properties such as virulence, sensitivity to antichagasic drugs, transmission cycles, pathogenicity and tropism. Being TcI involved in one of the two major hybridization events, it is important to focus in these new four described haplotypes. Thus, the purpose of our investigation is to provide more biological, genetic and immunological evidences of the existence of the wide heterogeneity between T. cruzi TcI (DTU I) strains. In this study, by the sequencing the miniexon intergenic region we observed a certain genetic variability in the T. cruzi TcI strains that belong to the haplotypes Ia, Ib and Id. Moreover, using a murine experimental model of infection (Balb/c strain), differences were observed in the pattern of the humoral response generated during the late phase of infection (chronic phase of the disease) as well as in the tissue tropism among TcI strains under study. The data obtained suggests a possible correlation between the genotypic variability of TcI strains and their pathogenic capability.
References:
1. Macedo, A.M., et al., Trypanosoma cruzi: genetic structure of populations and relevance of genetic variability to the pathogenesis of chagas disease. Mem Inst Oswaldo Cruz, 2004. 99(1): p. 1-12.
2. Miles, M.A., et al., Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas' disease in Amazonian Brazil. Nature, 1978. 272(5656): p. 819-21.
3. Tibayrenc, M., et al., Natural populations of Trypanosoma cruzi, the agent of Chagas disease, have a complex multiclonal structure. Proc Natl Acad Sci U S A, 1986. 83(1): p. 115-9.
4. Tibayrenc, M. and F.J. Ayala, The clonal theory of parasitic protozoa: 12 years on. Trends Parasitol, 2002. 18(9): p. 405-10.
5. Miles, M.A., et al., The molecular epidemiology and phylogeography of Trypanosoma cruzi and parallel research on Leishmania: looking back and to the future. Parasitology, 2009. 136(12): p. 1509-28.
6. Zingales, B., et al., A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Mem Inst Oswaldo Cruz, 2009. 104(7): p. 1051-4.
7. Sturm, N.R. and D.A. Campbell, Alternative lifestyles: the population structure of Trypanosoma cruzi. Acta Trop. 2010. 115(1-2): p. 35-43.
8. Falla, A., et al., Haplotype identification within Trypanosoma cruzi I in Colombian isolates from several reservoirs, vectors and humans. Acta Trop, 2009. 110(1): p. 15-21.
Six Discrete Typing Units (DTU) were successfully identified by Multi-Locus Enzyme Electrophoresis (MLEE), Random Amplification of Polymorphic DNA (RAPD) and by the analysis of the polymorphism rRNA and mini-exon gene sequences [5]. These DTUs are actually named from TcI to TcVI [6]. TcI and TcII are considered the parental phylogenetic lineages while the other DTUs seem to be the product of successive hybridization events [7]. However, recently, based on the analysis of the polymorphism of the miniexon gene’s intergenic partial region four haplotypes have been identified in the DTU-TcI (TcIa-Id) [8].
Mouse models have been used to characterize T. cruzi strains properties such as virulence, sensitivity to antichagasic drugs, transmission cycles, pathogenicity and tropism. Being TcI involved in one of the two major hybridization events, it is important to focus in these new four described haplotypes. Thus, the purpose of our investigation is to provide more biological, genetic and immunological evidences of the existence of the wide heterogeneity between T. cruzi TcI (DTU I) strains. In this study, by the sequencing the miniexon intergenic region we observed a certain genetic variability in the T. cruzi TcI strains that belong to the haplotypes Ia, Ib and Id. Moreover, using a murine experimental model of infection (Balb/c strain), differences were observed in the pattern of the humoral response generated during the late phase of infection (chronic phase of the disease) as well as in the tissue tropism among TcI strains under study. The data obtained suggests a possible correlation between the genotypic variability of TcI strains and their pathogenic capability.
References:
1. Macedo, A.M., et al., Trypanosoma cruzi: genetic structure of populations and relevance of genetic variability to the pathogenesis of chagas disease. Mem Inst Oswaldo Cruz, 2004. 99(1): p. 1-12.
2. Miles, M.A., et al., Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas' disease in Amazonian Brazil. Nature, 1978. 272(5656): p. 819-21.
3. Tibayrenc, M., et al., Natural populations of Trypanosoma cruzi, the agent of Chagas disease, have a complex multiclonal structure. Proc Natl Acad Sci U S A, 1986. 83(1): p. 115-9.
4. Tibayrenc, M. and F.J. Ayala, The clonal theory of parasitic protozoa: 12 years on. Trends Parasitol, 2002. 18(9): p. 405-10.
5. Miles, M.A., et al., The molecular epidemiology and phylogeography of Trypanosoma cruzi and parallel research on Leishmania: looking back and to the future. Parasitology, 2009. 136(12): p. 1509-28.
6. Zingales, B., et al., A new consensus for Trypanosoma cruzi intraspecific nomenclature: second revision meeting recommends TcI to TcVI. Mem Inst Oswaldo Cruz, 2009. 104(7): p. 1051-4.
7. Sturm, N.R. and D.A. Campbell, Alternative lifestyles: the population structure of Trypanosoma cruzi. Acta Trop. 2010. 115(1-2): p. 35-43.
8. Falla, A., et al., Haplotype identification within Trypanosoma cruzi I in Colombian isolates from several reservoirs, vectors and humans. Acta Trop, 2009. 110(1): p. 15-21.