Impact of clonal evolution on the biological diversity of Trypanosoma cruzi

Parasitology ◽  
1997 ◽  
Vol 114 (3) ◽  
pp. 213-218 ◽  
Author(s):  
J.-P. LAURENT ◽  
C. BARNABE ◽  
V. QUESNEY ◽  
S. NOEL ◽  
M. TIBAYRENC

Trypanosoma cruzi, the agent of Chagas' disease, exhibits considerable biological variability. Moreover, it has been postulated that populations of this protozoan are subdivided into natural clones, which can be separated from each other by considerable levels of evolutionary divergence. The authors have proposed that this long-term clonal evolution may have a profound impact on Trypanosoma cruzi biological diversity. In order to test this hypothesis, 16 T. cruzi stocks representing 3 major clonal genotypes of the parasite were analysed for 8 different in vitro biological parameters. The overall results show a strong statistical linkage between genetic and biological differences. This is in agreement with the working hypothesis, although a notable biological variability is observable among the stocks of each of the 3 major clonal genotypes. The authors propose that T. cruzi genetic variability must be taken into account in any applied study dealing with this parasite.

2005 ◽  
Vol 96 (6) ◽  
pp. 382-389 ◽  
Author(s):  
V. M. Veloso ◽  
A. J. Romanha ◽  
M. Lana ◽  
S. M. F. Murta ◽  
C. M. Carneiro ◽  
...  

2011 ◽  
Vol 53 (5) ◽  
pp. 247-253
Author(s):  
Leila Zalloum ◽  
Eliane Raquel Peres Lala ◽  
Neide Martins Moreira ◽  
Thaís Gomes Verzignassi Silveira ◽  
Márcia Machado de Oliveira Dalálio ◽  
...  

Twelve strains of Trypanosoma cruzi isolated from wild reservoirs, triatomines, and chronic chagasic patients in the state of Paraná, southern Brazil, and classified as T. cruzi I and II, were used to test the correlation between genetic and biological diversity. The Phagocytic Index (PI) and nitric-oxide (NO) production in vitro were used as biological parameters. The PI of the T. cruzi I and II strains did not differ significantly, nor did the PI of the T. cruzi strains isolated from humans, triatomines, or wild reservoirs. There was a statistical difference in the inhibition of NO production between T. cruzi I and II and between parasites isolated from humans and the strains isolated from triatomines and wild reservoirs, but there was no correlation between genetics and biology when the strains were analyzed independently of the lineages or hosts from which the strains were isolated. There were significant correlations for Randomly Amplified Polymorphic Deoxyribonucleic acid (RAPD) and biological parameters for T. cruzi I and II, and for humans or wild reservoirs when the lineages or hosts were considered individually.


2021 ◽  
Author(s):  
Gabriel Machado Matos ◽  
Michael D Lewis ◽  
Carlos Talavera-Lopez ◽  
Matthew Yeo ◽  
Edmundo C Grisard ◽  
...  

Protozoa and fungi are known to have extraordinarily diverse mechanisms of genetic exchange. However, the presence and epidemiological relevance of genetic exchange in Trypanosoma cruzi, the agent of Chagas disease, has been controversial and debated for many years. Field studies have identified both predominantly clonal and sexually recombining natural populations. Two of six natural T. cruzi lineages (TcV and TcVI) show hybrid mosaicism, using analysis of single-gene locus markers. The formation of hybrid strains in vitro has been achieved and this provides a framework to study the mechanisms and adaptive significance of genetic exchange. Using whole genome sequencing of a set of experimental hybrids strains, we have confirmed that hybrid formation initially results in tetraploid parasites. The hybrid progeny showed novel mutations that were not attributable to either (diploid) parent showing an increase in amino acid changes. In long-term culture, up to 800 generations, there was progressive, gradual erosion of progeny genomes towards triploidy, yet retention of elevated copy number was observed at several core housekeeping loci. Our findings indicate hybrid formation by fusion of diploid T. cruzi, followed by sporadic genome erosion, but with substantial potential for adaptive evolution, as has been described as a genetic feature of other organisms, such as some fungi.


2021 ◽  
Vol 14 (5) ◽  
pp. 419
Author(s):  
Rubén Martín-Escolano ◽  
Daniel Molina-Carreño ◽  
Daniel Plano ◽  
Socorro Espuelas ◽  
María J. Rosales ◽  
...  

Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the well-known extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent.


1992 ◽  
Vol 175 (1) ◽  
pp. 29-39 ◽  
Author(s):  
R R dos Santos ◽  
M A Rossi ◽  
J L Laus ◽  
J S Silva ◽  
W Savino ◽  
...  

The contribution of autoimmunity in the genesis of chronic Chagas' heart pathology is not clear. In the present study, we show that: (a) BALB/c mice chronically infected with Trypanosoma cruzi reject syngeneic newborn hearts; (b) in vivo treatment with anti-CD4 but not anti-CD8 monoclonal antibodies (mAbs) abrogates rejection; (c) CD4+ T cells from chronically infected mice proliferate in vitro to syngeneic myocardium antigens and induce heart graft destruction when injected in situ; (d) anti-CD4 treatment of chronically infected mice establishes long-term tolerance to syngeneic heart grafts; and (e) the state of tolerance is related to in vitro and in vivo unresponsiveness of the CD4+ T cells. These findings allow us to suggest that autoimmunity is the major mechanism implicated in the rejection of syngeneic heart tissues grafted into the pinna of the ear of mice chronically infected with T. cruzi. The similarity of the lesions to those found in humans suggests that autoimmunity is involved in the pathogenesis of chagasic cardiomyopathy in humans. Moreover, this could imply therapeutic strategies by reestablishing long-term tissue-specific tolerance with anti-CD4 mAb treatment, mediating anergy, or deleting the responder CD4+ T cells to heart tissue antigens.


Genomics ◽  
2016 ◽  
Vol 107 (6) ◽  
pp. 259-266 ◽  
Author(s):  
Fumio Kasai ◽  
Noriko Hirayama ◽  
Midori Ozawa ◽  
Masashi Iemura ◽  
Arihiro Kohara

2007 ◽  
Vol 102 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Paulo MM Guedes ◽  
Vanja M Veloso ◽  
Marcelo V Caliari ◽  
Cláudia M Carneiro ◽  
Sheler M Souza ◽  
...  

Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.


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