Population structure and genetic typing of Trypanosoma cruzi, the agent of Chagas disease: a multilocus enzyme electrophoresis approach

Parasitology ◽  
2000 ◽  
Vol 120 (5) ◽  
pp. 513-526 ◽  
Author(s):  
C. BARNABÉ ◽  
S. BRISSE ◽  
M. TIBAYRENC
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Natural Populations ◽  
Enzyme Electrophoresis ◽  
Strong Linkage Disequilibrium ◽  
Multilocus Enzyme Electrophoresis ◽  
Routine Identification ◽  
Genetic Clusters ◽  
Phylogenetic Lineages ◽  
The Impact

A set of 434 Trypanosoma cruzi stocks from a wide ecogeographical range was analysed by Multilocus Enzyme Electrophoresis for 22 genetic loci. Strong linkage disequilibrium, not associated with geographical distance, and 2 main genetic clusters each considerably heterogeneous, was observed. These results support the hypotheses previously proposed that T. cruzi natural populations are composed of highly diversified genetic clones distributed into 2 main phylogenetic lineages: lineage 1, the most ubiquitous in the endemic area, was more frequently observed in sylvatic cycles, whereas lineage 2, predominant in humans and domestic cycles, in the southern part of the area surveyed, was further partitioned into 5 lesser genetic subdivisions. T. cruzi appears therefore subdivided into at least 6 ‘discrete typing units’ or DTUs (Tibayrenc, 1998a–c). We have identified various specific isoenzyme markers (‘tags’; Tibayrenc, op. cit.) suitable for the routine identification of these DTUs for epidemiological tracking purposes. We discuss the correspondence with previous classifications and with the recent recommendations of the 90th anniversary of the discovery of Chagas disease symposium, as well as the impact of T. cruzi genetic variability on this parasite's biomedical diversity.

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

Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1509-1528 ◽  
Author(s):  
M. A. MILES ◽  
M. S. LLEWELLYN ◽  
M. D. LEWIS ◽  
M. YEO ◽  
R. BALEELA ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Molecular Epidemiology ◽  
Chagas Disease ◽  
Genetic Exchange ◽  
Sand Fly ◽  
Ecological Niches ◽  
Enzyme Electrophoresis ◽  
Multilocus Enzyme Electrophoresis ◽  
Genetic Groups

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.

Impact of number of isoenzyme loci on the robustness of intraspecific phylogenies using multilocus enzyme electrophoresis: consequences for typing of Trypanosoma cruzi

Parasitology ◽  
2003 ◽  
Vol 127 (3) ◽  
pp. 273-281 ◽  
Author(s):  
S. F. BRENIERE ◽  
C. BARNABE ◽  
M. F. BOSSENO ◽  
M. TIBAYRENC
Keyword(s):  
Trypanosoma Cruzi ◽  
Genetic Heterogeneity ◽  
Phylogenetic Diversity ◽  
Enzyme Electrophoresis ◽  
Phylogenetic Information ◽  
Bootstrap Analysis ◽  
Robust Clustering ◽  
Genetic Typing ◽  
Multilocus Enzyme Electrophoresis ◽  
The Impact

Thirty-one stocks of Trypanosoma cruzi, the agent of Chagas disease, representative of the genetic variability of the 2 principal lineages, that subdivide T. cruzi, were selected on the basis of previous multilocus enzyme electrophoresis analysis using 21 loci. Analyses were performed with lower numbers of loci to explore the impact of the number of loci on the robustness of the phylogenies obtained, and to identify the loci that have more impact on the phylogeny. Analyses were performed with numerical (UPGMA) and cladistical (Wagner parsimony analysis) methods for all sets of loci. Robustness of the phylogenies obtained was estimated by bootstrap analysis. Low numbers of randomly selected loci (6) were sufficient to demonstrate genetic heterogeneity among the stocks studied. However, they were unable to give reliable phylogenetic information. A higher number of randomly selected loci (15 and more) were required to reach this goal. All loci did not convey equivalent information. The more variable loci detected a greater genetic heterogeneity among the stocks, whereas the least variable loci were better for robust clustering. Finally, analysis was performed with only 5 and 9 loci bearing synapomorphic allozyme characters previously identified among larger samples of stocks. A set of 9 such loci was able to uncover both genetic heterogeneity among the stocks and to build robust phylogenies. It can therefore be recommended as a minimum set of isoenzyme loci that bring maximal information for all studies aiming to explore the phylogenetic diversity of a new set of T. cruzi stocks and for any preliminary genetic typing. Moreover, our results show that bootstrap analysis, like any statistics, is highly dependent upon the information available and that absolute bootstrap figures should be cautiously interpreted.

scholarly journals Genomics and High-Resolution Typing Confirm Predominant Clonal Evolution Down to a Microevolutionary Scale in Trypanosoma cruzi

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 356 ◽  
Author(s):  
Michel Tibayrenc ◽  
Francisco J. Ayala
Keyword(s):  
High Resolution ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Genetic Recombination ◽  
Phylogenetic Signal ◽  
Clonal Evolution ◽  
Natural Populations ◽  
Evolutionary Patterns ◽  
The Impact ◽  
Evolutionary Units

Trypanosoma cruzi, the agent of Chagas disease, is a paradigmatic case of the predominant clonal evolution (PCE) model, which states that the impact of genetic recombination in pathogens’ natural populations is not sufficient to suppress a persistent phylogenetic signal at all evolutionary scales. In spite of indications for occasional recombination and meiosis, recent genomics and high-resolution typing data in T. cruzi reject the counterproposal that PCE does not operate at lower evolutionary scales, within the evolutionary units (=near-clades) that subdivide the species. Evolutionary patterns in the agent of Chagas disease at micro- and macroevolutionary scales are strikingly similar (“Russian doll pattern”), suggesting gradual, rather than saltatory evolution.

Trypanosoma cruzi Discrete Typing Units in Chagas disease patients from endemic and non-endemic regions of Argentina

Parasitology ◽  
2012 ◽  
Vol 139 (4) ◽  
pp. 516-521 ◽  
Author(s):  
C. I. CURA ◽  
R. H. LUCERO ◽  
M. BISIO ◽  
E. OSHIRO ◽  
L. B. FORMICHELLI ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Natural Populations ◽  
Clinical Samples ◽  
Kidney Transplant Patient ◽  
Tissue Samples ◽  
Cardiac Tissues ◽  
Taxonomical Status ◽  
Immunosuppressed Patients ◽  
History Of

SUMMARYGenetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.

Molecular karyotype and schizodeme analyses of Trypanosoma cruzi stocks from Chilean triatomines

Parasitology ◽  
1997 ◽  
Vol 115 (1) ◽  
pp. 41-46 ◽  
Author(s):  
J. VENEGAS ◽  
S. ORTIZ ◽  
S. MUNOZ ◽  
A. SOLARI
Keyword(s):  
Trypanosoma Cruzi ◽  
Southern Blotting ◽  
Clonal Propagation ◽  
Triatoma Infestans ◽  
Pulse Field ◽  
Enzyme Electrophoresis ◽  
Kinetoplast Dna ◽  
Pulse Field Gel Electrophoresis ◽  
Multilocus Enzyme Electrophoresis ◽  
Molecular Karyotype

Forty-one Trypanosoma cruzi stocks isolated from the Chilean vectors Triatoma infestans and Triatoma spinolai were characterized by pulse-field gel electrophoresis and Southern blotting with the cruzipain gene, and by schizodeme analysis of kinetoplast DNA with EcoRI and Msp I. Seven parasite groups were found by molecular karyotype which correlate with schizodeme and multilocus enzyme electrophoresis, supporting the concept of clonal propagation for Trypanosoma cruzi. A predominant T. cruzi stock was isolated from domiciliary T. infestans in several geographical areas of Chile. In contrast, other frequently found genotypes were circulating in the sylvatic and domestic transmission cycles of specific geographical areas. The greatest heterogeneity of T. cruzi stocks was found among sylvatic T. spinolai where at least 4 genotypes were obtained from a sample of 16 T. cruzi stocks.

scholarly journals Synthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity Relationship versus the Parasite Cysteine Proteases Rhodesain, Cruzain, and Schistosoma mansoni Cathepsin B1

2015 ◽  
Vol 59 (5) ◽  
pp. 2666-2677 ◽  
Author(s):  
Nayara Cristina Fonseca ◽  
Luana Faria da Cruz ◽  
Filipe da Silva Villela ◽  
Glaécia Aparecida do Nascimento Pereira ◽  
Jair Lage de Siqueira-Neto ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Schistosoma Mansoni ◽  
Trypanosoma Brucei ◽  
Chagas Disease ◽  
Cysteine Proteases ◽  
Content Type ◽  
Structure Activity ◽  
Biochemical Assays ◽  
The Impact

ABSTRACTThe pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, andSchistosoma mansoniCB1 (SmCB1), the major cysteine proteases fromTrypanosoma cruzi,Trypanosoma brucei, andS. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50= 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluatedin vitroagainst the parasitesT. cruzi,T. brucei, andS. mansoni, revealing active compounds among this series.

scholarly journals The economic value of identifying and treating Chagas disease patients earlier and the impact on Trypanosoma cruzi transmission

2018 ◽  
Vol 12 (11) ◽  
pp. e0006809 ◽  
Author(s):  
Sarah M. Bartsch ◽  
Cameron M. Avelis ◽  
Lindsey Asti ◽  
Daniel L. Hertenstein ◽  
Martial Ndeffo-Mbah ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Economic Value ◽  
The Impact
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