Thetrans-sialidase, the majorTrypanosoma cruzivirulence factor: Three decades of studies

Abstract

Chagas' disease is a potentially life-threatening disease caused by the protozoan parasite Trypanosoma cruzi. Since the description of Chagas'disease in 1909 extensive research has identified important events in the disease in order to understand the biochemical mechanism that modulates T. cruzi-host cell interactions and the ability of the parasite to ensure its survival in the infected host. Exactly 30 years ago, we presented evidence for the first time of a trans-sialidase activity in T. cruzi (T. cruzi-TS). This enzyme transfers sialic acid from the host glycoconjugates to the terminal β-galactopyranosyl residues of mucin-like molecules on the parasite's cell surface. Thenceforth, many articles have provided convincing data showing that T. cruzi-TS is able to govern relevant mechanisms involved in the parasite's survival in the mammalian host, such as invasion, escape from the phagolysosomal vacuole, differentiation, down-modulation of host immune responses, among others. The aim of this review is to cover the history of the discovery of T. cruzi-TS, as well as some well-documented biological effects encompassed by this parasite's virulence factor, an enzyme with potential attributes to become a drug target against Chagas disease.

Unraveling Chagas disease transmission through the oral route: Gateways to Trypanosoma cruzi infection and target tissues

“…cruzi , due to its ability to reduce host cell immune response and mediate T . cruzi and host cells adhesion [55]. It has been shown that transialidase have adhesive capacity with host sialoglycans, generating “eat me” signals in epithelial cells, facilitating the parasite entry into non-phagocytic cells [56].…”

A Brief View of the Surface Membrane Proteins fromTrypanosoma cruzi

“…This group is included in the TS superfamily because it contains the conserved motif VTVxNVxLYNR, which is shared by all known TS members [10, 37, 54, 61, 115]. However, the B5 peptide from TsTc13 protein, a representative of Group IV, has been shown to be highly antigenic and is present in the infective metacyclic trypomastigote form [49].…”

Trypanosoma cruzi contains two galactokinases; molecular and biochemical characterization

“…In that location, there is no glucose availability, however the parasites maintain their cellular surface covered with glycoconjugates rich in terminal β-galactopyranosyl residues, with attached the sialic acid transferred from host cells. These glycoconjugates are involved in the parasite's survival in the mammalian host [45,46]. In contrast, TcGALK-1 could operate in a condition with a high ATP/ADP ratio, where TcGALK-2 is inhibited by its nucleotide substrate and TcGALK-1 is active.…”