Role of the gp85/Trans-Sialidase Superfamily of Glycoproteins in the Interaction of Trypanosoma cruzi with Host Structures

Abstract

I nvasion of mammalian cells by 77 cruzi trypomastigotes Is a multi-step and complex process involving several adhesion molecules, signaling events and proteolytic activities.From the blood to the cell target in different tissues the parasite has to interact with differ› ent cells and the extracellular matrix (ECM). The review focus on the role of the gp85/ trans-sialidase superfamily members in the interaction of the parasite with the host cell, par› ticularly with ECM components, with emphasis on the significant variability among the ligands and receptors involved. Use of the SELEX technique to evolve nuclease-resistant RNA ap tamers for receptor identification is briefly discussed.

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

“…Approximately 50% of the T. cruzi genome encodes a diversity of surface proteins, distributed into the gp63 proteases, the gp85/trans-sialidase superfamily (TS), the mucins, and the mucin-associated proteins (13,125). The long-standing adaptation of T. cruzi to vertebrate hosts has been credited to the structural and functional polymorphism of cysteine protease isoforms of the parasite cruzipain genes showing different substrate preferences and susceptibility inhibitors (119,237).…”

The gp82 Surface Molecule of Trypanosoma cruzi Metacyclic Forms

“…Tissue culture-derived trypomastigotes (TCT), which correspond to the parasite forms that circulate in the bloodstream and disseminate to diverse organs and tissues, express on the surface molecules of the gp85/ trans -sialidase superfamily ( Alves and Colli 2008 ). The structure of Tc85-11, a family member with laminin-binding property implicated in host cell invasion, has been determined (Giordano et al 1999 ;Marroquin-Quelopana et al 2004 ).…”

Drug Discovery by Aptamers in Protozoan Infectious Diseases

“…As already outlined the causing agent of Chagas' disease depends on invasion of host cells to complete its life cycle. Thereby the parasite needs to build up parasite-host cell adhesion for initiation of the invasion process (Alves and Colli, 2008). Macromolecules on host cell surfaces such as laminin, thrombospondin, heparan sulfate, and fibronectin are believed to be involved in parasite-host cell contact , Simmons et al, 2006.…”

“…The SELEX technology was employed to evolve nuclease-resistant RNA aptamers which block in vitro receptor-ligand interactions between T. cruzi trypomastigotes and epithelial monkey kidney LLC-MK(2) cells and thereby partially inhibit cell invasion by the parasite . Aptamers were identified with binding affinities in the nanomolar range to parasite receptors expressed by infective trypomastigote and not by insect epimastigote forms for the host cell matrix molecules fibronectin, heparan sulphate, laminin and thrombospondin Alves and Colli, 2008). Reduction in the infection rate in vitro of up to 70 percent was observed at a low micromolar aptamer concentration.…”