Cloning, heterologous expression, and substrate specificities of protein farnesyltransferases from Trypanosoma cruzi and Leishmania major

2002 ◽  
Vol 122 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Frederick S Buckner ◽  
Richard T Eastman ◽  
José L Nepomuceno-Silva ◽  
Emily C Speelmon ◽  
Peter J Myler ◽  
...  
2000 ◽  
Vol 68 (5) ◽  
pp. 2728-2734 ◽  
Author(s):  
M. Belen Carrillo ◽  
Wenda Gao ◽  
Macario Herrera ◽  
Joseph Alroy ◽  
Jeffrey B. Moore ◽  
...  

ABSTRACT Earlier studies showed that mice primed for a few hours with thetrans-sialidase (TS) of Trypanosoma cruzi, the agent of Chagas' disease, become highly susceptible to trypanosomal infection. These studies suggest that TS affects parasite virulence independent of antigenic stimulation. Potentially, TS could enhance or reduce the virulence of heterologous microbes depending on the mechanism of TS action and on the type of immune response elicited by the particular parasite. We tested this hypothesis by expressing heterologous TS in Leishmania major, a protozoan parasite that causes cutaneous leishmaniasis and lacks TS and the TS product α2-3-linked sialic acid. Leishmania cells transfected with a T. cruzi TS expression construct made high levels of active enzyme, which was present in the promastigotes and shed into the extracellular milieu. TS expression did not affect L. majorbinding to and entry into cultured macrophages or its tropism for macrophage infection in vivo. However, TS-expressing L. major exhibited elevated virulence in BALB/c mice, as determined by lesion progression, parasite numbers, and macro- and microscopic examination of cutaneous lesions. Several genetic tests proved that the enhanced virulence was directly attributable to TS expression. The results are consistent with TS functioning to sabotage the mouse immune system to confer a growth advantage on T. cruzi and transgenic L. major. These data suggest that heterologous expression of T. cruzi virulence factors inLeishmania may provide a new approach for dissecting their function in vivo.


2020 ◽  
Vol 5 (3) ◽  
pp. 129
Author(s):  
Jose Luis Ramirez

On 15 July 2020 was the 15th anniversary of the Science Magazine issue that reported three trypanosomatid genomes, namely Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. That publication was a milestone for the research community working with trypanosomatids, even more so, when considering that the first draft of the human genome was published only four years earlier after 15 years of research. Although nowadays, genome sequencing has become commonplace, the work done by researchers before that publication represented a huge challenge and a good example of international cooperation. Research in neglected diseases often faces obstacles, not only because of the unique characteristics of each biological model but also due to the lower funds the research projects receive. In the case of Trypanosoma cruzi the etiologic agent of Chagas disease, the first genome draft published in 2005 was not complete, and even after the implementation of more advanced sequencing strategies, to this date no final chromosomal map is available. However, the first genome draft enabled researchers to pick genes a la carte, produce proteins in vitro for immunological studies, and predict drug targets for the treatment of the disease or to be used in PCR diagnostic protocols. Besides, the analysis of the T. cruzi genome is revealing unique features about its organization and dynamics. In this work, I briefly summarize the actions of Latin American researchers that contributed to the first publication of the T. cruzi genome and discuss some features of the genome that may help to understand the parasite’s robustness and adaptive capabilities.


1999 ◽  
Vol 43 (4) ◽  
pp. 985-987 ◽  
Author(s):  
John M. Kelly ◽  
Michael A. Miles ◽  
Anita C. Skinner

ABSTRACT We report here that bloodstream forms of the African trypanosome,Trypanosoma brucei, are sensitive to the anti-influenza virus drug rimantadine (50% inhibitory concentration of 1.26 μg ml−1 at pH 7.4). The activity is pH dependent and is consistent with a mechanism involving inhibition of the ability to regulate internal pH. Rimantadine is also toxic to the trypanosomatid parasites Trypanosoma cruzi and Leishmania major.


2015 ◽  
Vol 467 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Guilherme Rodrigo Reis Monteiro dos-Santos ◽  
Marcio Ribeiro Fontenele ◽  
Felipe de Almeida Dias ◽  
Pedro Lagerblad de Oliveira ◽  
José Luciano Nepomuceno-Silva ◽  
...  

Biochemistry ◽  
1988 ◽  
Vol 27 (10) ◽  
pp. 3776-3784 ◽  
Author(s):  
Raelene Grumont ◽  
Worachart Sirawaraporn ◽  
Daniel V. Santi

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