scholarly journals Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure.

2021 ◽  
Author(s):  
Gabriel Machado Matos ◽  
Michael D Lewis ◽  
Carlos Talavera-Lopez ◽  
Matthew Yeo ◽  
Edmundo C Grisard ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Single Gene ◽  
Natural Populations ◽  
Field Studies ◽  
Genetic Exchange ◽  
Diploid Parent ◽  
Hybrid Formation ◽  
Rapid Diversification

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.

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
Keyword(s):  
Trypanosoma Cruzi ◽  
Biological Diversity ◽  
Clonal Evolution ◽  
Evolutionary Divergence ◽  
Biological Variability ◽  
Profound Impact ◽  
Applied Study ◽  
Biological Differences

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.

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.

scholarly journals Induction of phagocytic activity and nitric-oxide production in natural populations of Trypanosoma Cruzi I and II from the state of Paraná, Brazil

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 ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Trypanosoma Cruzi ◽  
Deoxyribonucleic Acid ◽  
Biological Diversity ◽  
Natural Populations ◽  
The State ◽  
Phagocytic Index ◽  
No Production ◽  
Biological Parameters

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.

scholarly journals Development and Field Validation of Lidocaine-Loaded Castration Bands for Bovine Pain Mitigation

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2363
Author(s):  
James W. Saville ◽  
Joseph A. Ross ◽  
Tyler Trefz ◽  
Crystal Schatz ◽  
Heather Matheson-Bird ◽  
...  
Keyword(s):  
Field Studies ◽  
Tissue Samples ◽  
Management Procedures ◽  
Term Delivery ◽  
Kinetics Of ◽  
High Throughput Manner ◽  
Pain Mitigation

Castration is among the most common management procedures performed in the dairy and beef cattle industries and is mainly performed by surgery or elastic banding. Despite the various benefits of castration, all methods produce pain and distress. Castration by banding is simple, inexpensive, produces fewer complications, and can be performed in a high-throughput manner. Because lidocaine, a local anesthetic, can be delivered to trauma sites topically, we have formulated lidocaine-loaded castration bands (LLBs) to deliver local pain relief to calves during banded castration. The initial lidocaine content of three band types developed was between 80 and 200 mg per band. The transfer kinetics of lidocaine into tissue was determined in vitro, indicating a rapid release for the first 30 min, followed by a slow release lasting at least 48 h. Furthermore, the lidocaine delivery and pain mitigation effects of these LLBs were compared to standard lidocaine injections in vivo. Field studies indicated that LLBs performed at least as well as lidocaine injections for short-term lidocaine delivery into tissues and pain mitigation. Moreover, LLBs significantly outperformed lidocaine injections for long-term delivery and pain mitigation. The concentrations of lidocaine in the LLB-treated tissue samples were generally in the range of 0.5–3.5 mg of lidocaine per gram of tissue and were overall highest after 6 h. Lidocaine-loaded elastration bands deliver therapeutic quantities of lidocaine into scrotal tissues over a period of at least seven days in cattle. This approach would provide long-term pain mitigation to the animals and, by avoiding surgery or the administration of injections, would also decrease the time and handling costs for the producer.

scholarly journals Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma Cruzi Mitochondrion

2021 ◽  
Vol 14 (5) ◽  
pp. 419
Author(s):  
Rubén Martín-Escolano ◽  
Daniel Molina-Carreño ◽  
Daniel Plano ◽  
Socorro Espuelas ◽  
María J. Rosales ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Health Concern ◽  
Dependent Manner ◽  
Pharmacological Activities ◽  
Selenium Compounds ◽  
Fast Acting

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.

scholarly journals Anti-CD4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi.

1992 ◽  
Vol 175 (1) ◽  
pp. 29-39 ◽  
Author(s):  
R R dos Santos ◽  
M A Rossi ◽  
J L Laus ◽  
J S Silva ◽  
W Savino ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Cd4 T Cells ◽  
Heart Tissue ◽  
Major Mechanism ◽  
Heart Graft ◽  
Heart Pathology

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.

scholarly journals Rapid Diagnostic Tests for Trypanosoma cruzi Infection: Field Evaluation of Two Registered Kits in a Region of Endemicity and a Region of Nonendemicity in Argentina

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
Constanza Lopez-Albizu ◽  
Emmaría Danesi ◽  
Pablo Piorno ◽  
Mariana Fernandez ◽  
Francisco García Campos ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Diagnostic Tests ◽  
Clinical Manifestations ◽  
Field Evaluation ◽  
Field Studies ◽  
Rapid Diagnostic Tests ◽  
Content Type ◽  
Remote Areas ◽  
Poor Access

ABSTRACT Infection by Trypanosoma cruzi (Chagas disease [ChD]) affects around 7 million people in the Americas, most of whom are unaware of their status due to lack of clinical manifestations and poor access to diagnosis. Rapid diagnostic tests (RDTs) are widely used for screening for different infections (HIV, hepatitis B, and syphilis), and their application for ChD would facilitate access to diagnosis, especially in remote areas where health services have scarce resources. We conducted a prospective intervention study in 2018 to evaluate in the field two in vitro RDTs for ChD, authorized by the National Administration of Medicaments, Aliments, and Medical Technologies of Argentina (ANMAT), in areas of endemicity and nonendemicity in Argentina. We recruited 607 volunteers older than 18 years in Salta province and the city of Buenos Aires. The RDTs Ab Standard Diagnostics SD Bioline (SD) and Check Chagas Wiener Lab (WL) were performed in situ with whole-blood samples, and confirmatory serology was done at a reference center. The rate of infection with T. cruzi was 17.8% (108/607). The SD test showed 97.2% sensitivity (95% confidence interval [CI], 93.5 to 100) and 91.7% specificity (95% CI, 96.2 to 99.2%), and the WL test showed 93.4% sensitivity (95% CI, 88.2 to 98.6%) and 99.1% specificity (95% CI, 91.9 to 100%). The sensitivity and specificity for the two RDTs tested were higher than previously reported. These results encourage the use of the tested RDTs in Salta province and for further field studies for the implementation of these RDTs in other epidemiological scenarios. This will be very important to improve access to diagnosis of Chagas and its clinical management as a neglected disease, especially in remote areas with health access barriers.

scholarly journals Long-term social dynamics drive loss of function in pathogenic bacteria

2015 ◽  
Vol 112 (34) ◽  
pp. 10756-10761 ◽  
Author(s):  
Sandra Breum Andersen ◽  
Rasmus Lykke Marvig ◽  
Søren Molin ◽  
Helle Krogh Johansen ◽  
Ashleigh S. Griffin
Keyword(s):  
Social Interactions ◽  
Pathogenic Bacteria ◽  
Social Dynamics ◽  
Natural Populations ◽  
Population Level ◽  
Evolutionary Change ◽  
Bacterial Cells ◽  
Loss Of Function

Laboratory experiments show that social interactions between bacterial cells can drive evolutionary change at the population level, but significant challenges limit attempts to assess the relevance of these findings to natural populations, where selection pressures are unknown. We have increasingly sophisticated methods for monitoring phenotypic and genotypic dynamics in bacteria causing infectious disease, but in contrast, we lack evidence-based adaptive explanations for those changes. Evolutionary change during infection is often interpreted as host adaptation, but this assumption neglects to consider social dynamics shown to drive evolutionary change in vitro. We provide evidence to show that long-term behavioral dynamics observed in a pathogen are driven by selection to outcompete neighboring conspecific cells through social interactions. We find thatPseudomonas aeruginosabacteria, causing lung infections in patients with cystic fibrosis, lose cooperative iron acquisition by siderophore production during infection. This loss could be caused by changes in iron availability in the lung, but surprisingly, we find that cells retain the ability to take up siderophores produced by conspecifics, even after they have lost the ability to synthesize siderophores. Only when cooperative producers are lost from the population is the receptor for uptake lost. This finding highlights the potential pitfalls of interpreting loss of function in pathogenic bacterial populations as evidence for trait redundancy in the host environment. More generally, we provide an example of how sequence analysis can be used to generate testable hypotheses about selection driving long-term phenotypic changes of pathogenic bacteria in situ.

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