The revised Trypanosoma cruzi subspecific nomenclature: Rationale, epidemiological relevance and research applications

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Avenida Professor Lineu Prestes 748, 05508-000 São Paulo, SP, Brazil.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases (Impact Factor: 3.02). 03/2012; 12(2):240-53. DOI: 10.1016/j.meegid.2011.12.009
Source: PubMed


The protozoan Trypanosoma cruzi, its mammalian reservoirs, and vectors have existed in nature for millions of years. The human infection, named Chagas disease, is a major public health problem for Latin America. T. cruzi is genetically highly diverse and the understanding of the population structure of this parasite is critical because of the links to transmission cycles and disease. At present, T. cruzi is partitioned into six discrete typing units (DTUs), TcI-TcVI. Here we focus on the current status of taxonomy-related areas such as population structure, phylogeographical and eco-epidemiological features, and the correlation of DTU with natural and experimental infection. We also summarize methods for DTU genotyping, available for widespread use in endemic areas. For the immediate future multilocus sequence typing is likely to be the gold standard for population studies. We conclude that greater advances in our knowledge on pathogenic and epidemiological features of these parasites are expected in the coming decade through the comparative analysis of the genomes from isolates of various DTUs.

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Available from: Michel Tibayrenc, Oct 04, 2015
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    • "DTUs differ in their geographical distribution , ecological niche, vector and reservoir hosts. TcV and TcVI are associated with Chagas disease in southern and central South America, whereas TcI is the most abundant and widely dispersed of all the T. cruzi DTUs in the Americas (Zingales et al., 2012). Each DTU can include multiple parasite strains which are more closely related to each other than to strains from other DTUs by the presence of common molecular markers. "
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    ABSTRACT: The aim of this paper is to discuss the main ecological interactions between the parasite Trypanosoma cruzi and its hosts, the mother and the fetus, leading to the transmission and development of congenital Chagas disease. One or several infecting strains of T. cruzi (with specific features) interact with: (i) the immune system of a pregnant woman whom responses depend on genetic and environmental factors, (ii) the placenta harboring its own defenses, and, finally, (iii) the fetal immune system displaying responses also susceptible to be modulated by maternal and environmental factors, as well as his own genetic background which is different from her mother. The severity of congenital Chagas disease depends on the magnitude of such final responses. The paper is mainly based on human data, but integrates also complementary observations obtained in experimental infections. It also focuses on important gaps in our knowledge of this congenital infection, such as the role of parasite diversity vs host genetic factors, as well as that of the maternal and placental microbiomes and the microbiome acquisition by infant in the control of infection. Investigations on these topics are needed in order to improve the programs aiming to diagnose, manage and control congenital Chagas disease. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    Acta tropica 08/2015; DOI:10.1016/j.actatropica.2015.07.016 · 2.27 Impact Factor
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    • "At the time of this revision, Tcbat was limited to a few Brazilian isolates, and its characterization was restricted to a few genes. Multilocus sequence typing was recommended to provide additional support for any putative new DTUs (Zingales et al., 2012). Since then, a large number of molecular markers have added support to Tcbat as an independent lineage of T. cruzi, closest to TcI (Pinto et al., 2012; Lima et al., 2012a; Ramírez et al., 2014a,b; Cosentino and Agüero, 2012; Caballero et al., 2015; Franco et al., 2015). "
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    ABSTRACT: Trypanosoma cruzi is a complex of phenotypically and genetically diverse isolates distributed in six discrete typing units (DTUs) designated as TcI-TcVI. Five years ago, T. cruzi isolates from Brazilian bats showing unique patterns of traditional ribosomal and spliced leader PCRs not clustering into any of the six DTUs were designated as the Tcbat genotype. In the present study, phylogenies inferred using SSU rRNA (small subunit of ribosomal rRNA), gGAPDH (glycosomal glyceraldehyde 3-phosphate dehydrogenase) and Cytb (cytochrome b) genes strongly supported Tcbat as a monophyletic lineage prevalent in Brazil, Panama and Colombia. Providing strong support for Tcbat, sequences from 37 of 47 nuclear and 12 mitochondrial genes (retrieved from a draft genome of Tcbat) and reference strains of all DTUs available in databanks corroborated Tcbat as an independent DTU. Consistent with previous studies, multilocus analysis of most nuclear genes corroborated the evolution of T. cruzi from bat trypanosomes its divergence into two main phylogenetic lineages: the basal TcII; and the lineage clustering TcIV, the clade comprising TcIII and the sister groups TcI-Tcbat. Most likely, the common ancestor of Tcbat and TcI was a bat trypanosome. However, the results of the present analysis did not support Tcbat as the ancestor of all DTUs. Despite the insights provided by reports of TcIII, TcIV and TcII in bats, including Amazonian bats harbouring TcII, further studies are necessary to understand the roles played by bats in the diversification of all DTUs. We also demonstrated that in addition to value as molecular markers for DTU assignment, Cytb, ITS rDNA and the spliced leader (SL) polymorphic sequences suggest spatially structured populations of Tcbat. Phylogenetic and phylogeographical analyses, multiple molecular markers specific to Tcbat, and the degrees of sequence divergence between Tcbat and the accepted DTUs strongly support the definitive classification of Tcbat as a new DTU.
    Acta tropica 07/2015; DOI:10.1016/j.actatropica.2015.07.015 · 2.27 Impact Factor
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    • "-The sensitivity to BZ was determined in epimastigote forms of eight strains belonging to four DTUs (TcI, TcII, TcV and TcVI) (Table I). These DTUs are predominant in Chagas disease patients in different regions of Latin America (Miles et al. 2009, Zingales et al. 2012). We observed up to five-fold variation of the IC 50 values to BZ among the strains (115 strain, 7.6 ± 1.6 μM; YuYu strain, 40.5 ± 1.8 μM). "
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    ABSTRACT: 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.
    Memórias do Instituto Oswaldo Cruz 04/2015; 110(ahead). DOI:10.1590/0074-02760140407 · 1.59 Impact Factor
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