The molecular epidemiology and phylogeography of Trypanosoma cruzi and parallel research on Leishmania: looking back and to the future

Abstract

SUMMARYTrypanosoma cruzi is the protozoan agent of Chagas disease, and the most important parasitic disease in Latin America. Protozoa of the genus Leishmania are global agents of visceral and cutaneous leishmaniasis, fatal and disfiguring diseases. In the 1970s multilocus enzyme electrophoresis demonstrated that T. cruzi is a heterogeneous complex. Six zymodemes were described, corresponding with currently recognized lineages, TcI and TcIIa-e – now defined by multiple genetic markers. Molecular epidemiology has substantially resolved the phylogeography and ecological niches of the T. cruzi lineages. Genetic hybridization has fundamentally influenced T. cruzi evolution and epidemiology of Chagas disease. Genetic exchange of T. cruzi in vitro involves fusion of diploids and genome erosion, producing aneuploid hybrids. Transgenic fluorescent clones are new tools to elucidate molecular genetics and phenotypic variation. We speculate that pericardial sequestration plays a role in pathogenesis. Multilocus sequence typing, microsatellites and, ultimately, comparative genomics are improving understanding of T. cruzi population genetics. Similarly, in Leishmania, genetic groups have been defined, including epidemiologically important hybrids; genetic exchange can occur in the sand fly vector. We describe the profound impact of this parallel research on genetic diversity of T. cruzi and Leishmania, in the context of epidemiology, taxonomy and disease control.

Trypanosoma cruzi I genotype among isolates from patients with chronic Chagas disease followed at the Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ, Brazil)

“…The high genetic variability of T. cruzi has been confirmed by different approaches, and this species was classified in different sub-groups, as zymodemes 6,7,9 , major groups or lineages 10,11 , and thereafter in six discrete typing units (DTUs) 12 , which correspond to the six clusters of isozyme genotypes found by Tibayrenc and Ayala 13 . According to consensus among specialists, the main T. cruzi genetic types were correlated to those six DTUs, and they were renamed Trypanosoma cruzi I-VI (TcI-TcVI) 7,14,15 . Subsequently, a new genotype closely related to TcI was described in Brazilian bats 16 and named Tcbat or TcVII, although without consensus regarding its DTU assignment 8,17,18 .…”

“…Trypanosoma cruzi is composed of heterogeneous populations of the parasite that circulate among humans, vectors, domestic animals and wild reservoirs [6][7][8] . The high genetic variability of T. cruzi has been confirmed by different approaches, and this species was classified in different sub-groups, as zymodemes 6,7,9 , major groups or lineages 10,11 , and thereafter in six discrete typing units (DTUs) 12 , which correspond to the six clusters of isozyme genotypes found by Tibayrenc and Ayala 13 .…”

Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population structure, hybridization and a role for humans in Andean parasite dispersal

“…2009), which have distributions loosely defined by geography, ecology and transmission cycle (Miles et al . 2009). The level of nuclear sequence divergence between major T. cruzi DTUs is equivalent to interspecies diversity among New World Leishmania species (Yeo et al .…”

The role of humoral autoimmunity in gastrointestinal neuromuscular diseases

“…Phenotypically, chronic disease manifestations vary geographically, reflecting the heterogeneity of T.cruzi strains and their pathogenic sequalae. Megaoesophagus and megacolon are prominent complications in southern countries of South America, whereas these complications are rarer in Central and northern regions (Miles et al 2009). …”

“…It is now known that Trypanosoma cruzi (T.cruzi) is a heterogeneous organism, consisting of several strains (Miles et al 2009), and whilst host factors must also play a role, differences in infecting genotypes appear to govern chronic disease sequalae ( Figure 4.1). It is then likely that the patients in the present cohort were infected by a genotypically different organism to those studied previously, and although patients studied here and previously had GI involvement, the failure to detect anti-M 2 mAChR autoantibodies in our cohort may be due to a different immune response which is consequent of a dissimilar infective event.…”