Trypanosoma cruzi: mixture of two populations can modify virulence and tissue tropism in rat

Franco, D J; Vágó, A; Chiari, Égler; Meira, Fidel; Galvão, Lúcia Maria da Cunha; Machado, Conceição R. S.

doi:10.1016/s0014-4894(03)00119-x

Cited by 39 publications

(33 citation statements)

References 27 publications

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“…This lowlevel parasitemia is in agreement with previous findings at the acute timepoint used for analysis. While others have reported parasite distribution to lung, spleen and liver in cases when animals have been immunosuppressed (Calabrese et al, 1992) and even parasitism of bone and cartilage (Morocoima et al, 2006), it has become increasingly clear from a number of studies that the genetics of the parasite and host play a defining role in the tissue distribution of T. cruzi (Melo and Brener, 1978;Ben Younes-Chennoufi et al, 1988;McCabe et al, 1989;Andrade et al, 2002;Franco et al, 2003;Marinho et al, 2004). Although the pathogenesis of Chagas disease is multivariate, the persistence of T. cruzi has been suggested as playing a fundamental role in disease progression (Anez et al, 1999;Zhang and Tarleton, 1999;Tarleton, 2001).…”

Section: Discussionmentioning

confidence: 99%

Bioluminescent imaging of Trypanosoma cruzi infection

Hyland

Asfaw

Olson

et al. 2008

International Journal for Parasitology

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Chagas disease, caused by infection with the protozoan parasite Trypanosoma cruzi, is a major public health problem in Central and South America. The pathogenesis of Chagas disease is complex and the natural course of infection is not completely understood. The recent development of bioluminescence imaging technology has facilitated studies of a number of infectious and noninfectious diseases. We developed luminescent T. cruzi to facilitate similar studies of Chagas disease pathogenesis. Luminescent T. cruzi trypomastigotes and amastigotes were imaged in infections of rat myoblast cultures, which demonstrated a clear correlation of photon emission signal strength to the number of parasites used. This was also observed in mice infected with different numbers of luminescent parasites, where a stringent correlation of photon emission to parasite number was observed early at the site of inoculation, followed by dissemination of parasites to different sites over the course of a 25 day infection. Whole animal imaging from ventral, dorsal and lateral perspectives provided clear evidence of parasite dissemination. The tissue distribution of T. cruzi was further determined by imaging heart, spleen, skeletal muscle, lungs, kidneys, liver and intestines ex vivo. These results illustrate the natural dissemination of T. cruzi during infection and unveil a new tool for studying a number of aspects of Chagas disease, including rapid in vitro screening of potential therapeutic agents, roles of parasite and host factors in the outcome of infection, and analysis of differential tissue tropism in various parasite-host strain combinations.

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Section: Discussionmentioning

confidence: 99%

Bioluminescent imaging of Trypanosoma cruzi infection

Hyland

Asfaw

Olson

et al. 2008

International Journal for Parasitology

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“…In the heart, the L16 clone displayed a slight, nonsignificant trend toward less aggressiveness relative to the WT CL Brenner strain without significant differences in the real-time PCR quantitation. The 30-fold higher density of parasites observed between skeletal muscle and cardiac tissues also points to the tissue tropism of the T. cruzi strain or lineage (12,14,16). Indeed, this feature could explain the lack of significance found when WT and L16 parasitic loads were compared in cardiac tissue samples.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Infectivity and Immunoprotective Effect of a LYT1 Null Mutant of Trypanosoma cruzi

et al. 2008

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Trypanosoma cruzi is the causative agent of Chagas' disease and infects an estimated 18 million people in the American continents (27). This protozoan parasite is transmitted by three main routes: via the feces of infected triatomine insects, via blood transfusions, and from mother to fetus during pregnancy. Parasites persist through the entire life of the patient, and the disease normally progresses from an acute stage characterized only by systemic parasitemia to a virtually asymptomatic stage that can last for several decades. Eventually, onethird of chronically infected patients manifest symptoms of Chagas' disease, developing severe cardiac and/or gastrointestinal disease, which leads to death in most cases. Nowadays there is neither an effective cure nor a vaccine against T. cruzi infection, and the only methods for combating the disease are the control of the vector in areas of endemicity and the prevention of transmission via blood supply.The invasion of host cells by T. cruzi involves several steps: attachment of the parasite to the cell surface, internalization mediated by the recruitment and fusion of host cell lysosomes, and escape of the parasite from the parasitophorous vacuole to multiply freely in the cytosol as amastigotes (2,3,26). Though many parasite proteins are very important for T. cruzi infection, surprisingly, only a few have been identified experimentally. One parasite factor likely involved in the infection is the protein product of the LYT1 gene. Manning-Cela et al. (22) isolated a LYT1 cDNA clone from a Y strain T. cruzi amastigote library by virtue of its cross-reactivity to antibodies against the human complement component C9. On this basis, the researchers proposed that the 552-amino-acid protein encoded by the LYT1 open reading frame could be involved in a lytic pathway, mediating the escape of T. cruzi from the acidic parasitophorous vacuole into the cytosol, as was previously shown for the T. cruzi protein Tc-TOX with pore-forming activity at a low pH (4). However, a bioinformatics analysis of all available DNA and protein databases failed to identify paralogs. To gain insight into the possible role of the LYT1 gene product, the researchers generated a biallelic, LYT1 deletion in the CL strain and the biological characteristics of a mutant clone (clone L16) were assessed. The deletion of both alleles did not impair the capacity of epimastigote parasites to proliferate in axenic cultures. Nevertheless, the LYT1 null parasites exhibited reduced infectivity in cell culture experiments and also displayed accelerated in vitro-stage transition and diminished hemolytic activity at an acidic pH (23). These distinct phenotypes were attributed to the fact that different forms of the protein are expressed as a result of alternative trans splicing. Through this genetic regulation process of the primary transcript, two LYT1 protein derivates were obtained, differing only in the presence or absence of the first 28 amino acids. The trans-splicing processing was developmentally regulated, sinc...

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“…Sin embargo, este número de clones puede cambiar drásticamente a medida que trascurre el tiempo de infección, ya que en la fase crónica de la enfermedad ciertos clones del parásito son eliminados probablemente como resultado de factores inmunológicos del hospedero o debido a la capacidad de multiplicación o requerimientos nutricionales de cada clon (30). En el presente trabajo, mediante una infección mixta de clones pertenecientes a los dos grupos de T. cruzi, se simularon las condiciones de una infección natural en el modelo murino, permitiendo entender varios aspectos de la enfermedad, entre ellos, cuál es el genotipo causante de un tropismo específico y cuál de estos predomina en el hospedero después de un largo periodo de infección.…”

Section: Discussionunclassified

Caracterización biológica y genética de dos clones pertenecientes a los grupos I y II de Trypanosoma cruzi de Colombia

Botero¹,

Mejía²,

Triana³

2007

biomedica

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Introducción. T. cruzi I y T. cruzi II son grupos genéticamente diferentes y se cree que dicha variabilidad es determinante del tropismo tisular en el hospedero vertebrado y responsable de las diversas manifestaciones clínicas de la enfermedad de Chagas. Objetivo. Caracterizar biológica y genéticamente dos clones colombianos de los grupos T. cruzi I y II en el modelo murino. Materiales y métodos. Las cepas CAS15 y AF1 pertenecientes a los grupos T. cruzi I y II fueron clonadas en medio semisólido. Un clon de cada una de ellas y una mezcla de ambos se utilizaron para infectar ratones, los cuales se sacrificaron a diferentes tiempos post-infección. Para analizar la presencia del parásito en sangre y diferentes órganos, se utilizaron el microhematocrito y la reacción en cadena de la polimerasa con los marcadores de la secuencia satélite del ADN nuclear y con el espaciador intergénico del gen mini-exón. Resultados. El clon T. cruzi I fue más infectivo, observándose un tropismo preferencial por corazón, recto y músculo esquelético, mientras que el clon T. cruzi II presentó un tropismo preferencial por bazo e hígado. Durante la infección con la mezcla de los clones, se observó que el clon T. cruzi I predominó sobre el T. cruzi II tanto en sangre como en órganos. Conclusiones. Los resultados confirman que las diferencias genéticas entre los grupos de T. cruzi podrían estar determinando el tropismo tisular y de esta manera jugar un papel fundamental en el entendimiento de las manifestaciones clínicas de la enfermedad de Chagas en Colombia.Palabras claves: Trypanosoma cruzi, enfermedad de Chagas, variación (Genética), tropismo. Biological and genetic characterization of two Colombian clones of Trypanosoma cruzi groups I and IIIntroduction. Genetic differences between T. cruzi I and T. cruzi II may determine differences in their tissue tropism in the vertebrate host and may also be responsible for the differences in clinical manifestations of Chagas disease. Objective. Two Colombian clones of the T. cruzi groups I and II were characterized biologically and genetically in a murine model. Materials and methods. Strains Cas15 and AF1 belonging to the T. cruzi groups I and II were cloned in semisolid medium. A clone of each strain and a mix of both were used to infect mice; the mice were subsequently sacrificed at selected post-infection intervals. In order to identify the parasite presence in blood and organs, two methods were used (a) microhematocrit and (b) polymerase chain reaction with primers for satellite DNA and the intergenic region of miniexon. Results. The T. cruzi I clone was more infectious, with a preferential tropism observed in heart, rectum and skeletal muscle, whereas clone T. cruzi II exhibited a preferential tropism for spleen and liver. During the infection with the clone mixture a predominance of the T. cruzi I clone over clone II in blood as well as in organs was observed. Conclusion. The results corroborate that the genetic differences between the T. cruzi groups correlate with their tissue tropism, an...

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Trypanosoma cruzi: mixture of two populations can modify virulence and tissue tropism in rat

Cited by 39 publications

References 27 publications

Bioluminescent imaging of Trypanosoma cruzi infection

Bioluminescent imaging of Trypanosoma cruzi infection

Impairment of Infectivity and Immunoprotective Effect of a LYT1 Null Mutant of Trypanosoma cruzi

Caracterización biológica y genética de dos clones pertenecientes a los grupos I y II de Trypanosoma cruzi de Colombia

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