Chagas is an incurable, chronic debilitating, and deadly disease affecting many millions of people in Latin America. It is caused by the protozoan Trypanosoma cruzi. The molecular mechanism governing T. cruzi- host interaction is not completely understood. In the last few years several molecules were identified in T. cruzi that are potential mediators of parasite-host interaction. Of these molecules, the most promising and best characterized is the trans- sialidase expressed by infective forms of T. cruzi. The enzyme is located on the surface of the parasite an is readily released into the extracellular environment. It desialylates and re-sialylates host glycoconjugates in solution and on cell surfaces of the parasite and is readily released into the extracellular environment. It desialylates and re-sialylates host glycoconjugates in solution and on cell surfaces. It interacts with extracellular matrix that surrounds cells in tissues. The purified enzyme greatly enhances the virulence of T. cruzi for experimental animals. In contrasts, abrogates the course of infection in vivo. The trans-sialidase may also affect host cell function, such as those of neurons. The studies proposed here are designed to extend these observations and to gain further insights into the structure function relationship of the enzyme. Further goals include a determination of the potential of the trans-sialidase as a vaccine and as a pathology determinant in Chagas. The goals of this project are to study the substrate and enzymatic properties of the enzyme, as well as enzyme interaction with the extracellular matrix. Dissections of the role the trans-sialidase play in infection will include an analysis of T. cruzi penetration in the basement membrane and host cells. A possible harmful effect of the outgrowth. The holoenzyme, its substrate, and peptides derived from various domains of the trans-sialidase, will be tested for alteration of the course of infection in mice.
| Ortega-Barria, E; Pereira, M E (1992) Entry of Trypanosoma cruzi into eukaryotic cells. Infect Agents Dis 1:136-45 |
