Study of inactive trans-sialidase enzyme of trypomastigotes as a virulent factor for Trypanosoma cruzi infection. role of inactive trans-sialidase in pathogenesis of Trypanosoma cruzi

Trypanosoma cruzi, the agent of Chagas disease, is unable to synthetize sialic acids de novo, this sugar is acquired by the trans-sialidase (TS), an enzime that is relevant in pathogenesis and in the parasite biology. Genes encoding TS are included into a superfamily of antigens, TS family contain 150 genes, 50% of them encode for the active enzyme (TSa) and the other 50% for an inactive TS (TSi). The inactivation is due to the single replacement Tyr342His, but TSi retain the substrate binding ability having therefore a lectin-like function. We studied the biological role of TSi isoforms since its remains controversial. To this aim we have analyzed different T.cruzi strains observing that lethal strains contain similar proportions TSa/TSi gene types and that low virulence strains contain only TSa genes. Since the most aggressive parasites all contain genes encoding for the iTS isoform, it can be proposed a role for this protein in the virulent behavior. The fact that genes encoding TSi are absent in low T.cruzi strains, will allow us to insert tagged its genes into this parasite genome to analyze their actual relevance in virulence by employing in vitro and in vivo assays