Sequence diversity and differential expression of Tc52 immuno-regulatory protein in Trypanosoma cruzi: potential implications in the biological variability of strains

Mathieu-Daudé, Françoise; Bosseno, Marie-France; Garzón, Edwin; Lelièvre, Joël; Sereno, Denis; Ouaissi, Ali; Brenière, Simone Frédérique

doi:10.1007/s00436-007-0651-3

Cited by 14 publications

(12 citation statements)

References 37 publications

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“…Natural populations of T. cruzi are very heterogeneous in biological, biochemical, immunological, and molecular features (Miles 2003;Dost et al 2004;Mathieu-Daudé et al 2007;Santos-Mallet et al 2008;Venegas et al 2010); consequently, different strains from endemic areas might be responsible for distinct clinical manifestations and chemotherapy response (Andrade 1999). In this context, previous works reported that T. cruzi strains produced different amounts of proteases, including the major cysteine protease named cruzipain (Fampa et al 2008(Fampa et al , 2010Gomes et al 2009;Kikuchi et al 2010).…”

Section: Discussionmentioning

confidence: 96%

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

et al. 2011

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Herein, we have aimed to explore the effects of pepstatin A, a powerful aspartic protease inhibitor, on Trypanosoma cruzi, the etiologic agent of Chagas' disease. Pepstatin A arrested the proliferation of epimastigotes of T. cruzi (clone Dm28c, TcI lineage), in both dose- and time-dependent manner. The IC(50) value was calculated to be 36.2 μM after 96 h of parasite-drug contact. The parasite treatment with pepstatin A resulted in significant morphological alterations, including parasites becoming round in shape, reduction (≈25%) of the parasite size, and parasites presenting parts or the whole flagellum detached from the cell body. Cell lysis was not observed, resulting in a trypanostatic effect. The treatment of different T. cruzi strains, belonging to distinct phylogenetic lineages, with pepstatin A at 36.2 μM resulted in growth inhibition as follows: 28% to Y (TcII), 45% to CL Brener (TcII), 45.4% to 4167 (Z3), and 26.4% to 3663 (Z3) strains. The hydrolysis of a cathepsin D fluorogenic substrate (7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-D: -Arg-amide) by T. cruzi epimastigote extract was inhibited (≈65%) by pepstatin A at 10 μM, suggesting that an aspartic protease may be the intracellular target of this inhibitor. Curiously, pepstatin A induced an increase of 54% and 98%, respectively, in the surface expression of gp63- and calpain-related molecules in epimastigotes, but not in the cruzipain level, as well as stimulated the epimastigote-to-trypomastigote differentiation in a dose-dependent manner. However, approximately 45% of the trypomastigotes had their flagellum detached from the cell body. These results contribute to understand the possible role of aspartic proteases in the physiology of T. cruzi cells, adding new in vitro insights into the possibility of exploiting aspartic protease as promising targets to treat Chagas' disease.

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Section: Discussionmentioning

confidence: 96%

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

et al. 2011

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“…Despite its broad genetic diversity, three major lineages, named T. cruzi I, II and III, have been identified in the parasite population [81]. Studies with a number of molecular markers revealed that parasites belonging to the T. cruzi I lineage have lower genetic variability compared to T. cruzi II, and III [82–84]. The great genetic diversity observed in T. cruzi (and more precisely, in T. cruzi II strains) may play an important role in pathogenesis and survival of the parasite within its different hosts.…”

Section: Mismatch Repairmentioning

confidence: 99%

Overview of DNA Repair in Trypanosoma cruzi, Trypanosoma brucei, and Leishmania major

Passos‐Silva

Rajão

Aguiar

et al. 2010

Journal of Nucleic Acids

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A wide variety of DNA lesions arise due to environmental agents, normal cellular metabolism, or intrinsic weaknesses in the chemical bonds of DNA. Diverse cellular mechanisms have evolved to maintain genome stability, including mechanisms to repair damaged DNA, to avoid the incorporation of modified nucleotides, and to tolerate lesions (translesion synthesis). Studies of the mechanisms related to DNA metabolism in trypanosomatids have been very limited. Together with recent experimental studies, the genome sequencing of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, has revealed interesting features of the DNA repair mechanism in these protozoan parasites, which will be reviewed here.

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“…Metacyclic trypomastigotes, obtained from the differentiation of late stationary phase epimastigotes, were used to initiate infection of mouse fibroblasts (L929). Trypomastigotes and amastigotes were produced and harvested as previously described [12]. Pellets for RNA purification were processed immediately in lysis buffer.…”

Section: Methodsmentioning

confidence: 99%

An Experimental Approach for the Identification of Conserved Secreted Proteins in Trypanosomatids

Corrales

Mathieu-Daudé²,

Garcia³

et al. 2010

Journal of Biomedicine and Biotechnology

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Extracellular factors produced by Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei are important in the host-parasite relationship. Here, we describe a genome-based approach to identify putative extracellular proteins conserved among trypanosomatids that are likely involved in the classical secretory pathway. Potentially secreted proteins were identified by bioinformatic analysis of the T. cruzi genome. A subset of thirteen genes encoding unknown proteins with orthologs containing a signal peptide sequence in L. infantum, L. major, and T. brucei were transfected into L. infantum. Tagged proteins detected in the extracellular medium confirmed computer predictions in about 25% of the hits. Secretion was confirmed for two L. infantum orthologs proteins using the same experimental system. Infectivity studies of transgenic Leishmania parasites suggest that one of the secreted proteins increases parasite replication inside macrophages. This methodology can identify conserved secreted proteins involved in the classical secretory pathway, and they may represent potential virulence factors in trypanosomatids.

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Sequence diversity and differential expression of Tc52 immuno-regulatory protein in Trypanosoma cruzi: potential implications in the biological variability of strains

Cited by 14 publications

References 37 publications

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

Overview of DNA Repair in Trypanosoma cruzi, Trypanosoma brucei, and Leishmania major

An Experimental Approach for the Identification of Conserved Secreted Proteins in Trypanosomatids

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