The objective of this proposal is to define some of the biochemical processes involved in the internalization of Toxoplasma gondii into the host cell. Devastating illness may develop in patients with AIDS. Reactivation of encysted bradyzoites in the central nervous system of persons with AIDS causes most of the cases of toxoplasmi.c encephalitis seen in this population. Advances in the area of cellular and molecular biology are critical since they will help to develop new antiparasitic compounds and provide better understanding of the pathogenesis of the disease. We have detected that upon association of T. gondii tachyzoites with culture macrophages, the host cells show an increase in the concentration of inositol phosphates and intracellular Ca2+ ([Ca2+]i). In addition, we have detected two important plasma membrane-associated phosphatase activities in tachyzoites that could be involved in host invasion, in the establishment of infection, or in the exit of the parasite from the infected host cell. One of these plasma membrane-associated phosphatases is apparently translocated into the macrophages plasma membrane and stimulated 2 to 4-fold upon association of tachyzoites. This activity is stimulated 8-fold if macrophages are pretreated with calcium ionophore A- 23187, thus indicating that (Ca2+]i) increases in the macrophages are important for this translocation and activation processes. Our plan is: (1) To characterize the plasma membrane-associated phosphatase activities of T. gondii tachyzoites (2) To identify the plasma membrane- associated phosphatase activity that is stimulated upon the interaction of tachyzoites with mammalian cells, (3) To investigate the role of plasma membrane-associated phosphatases in the processes of penetration, establishment of infection, and exit of the parasite from the infected host cell, and (4) To investigate the role of plasma membrane-associated phosphatases in the protection of T. gondii against host cell defense mechanisms.
| Vercesi, A E; Rodrigues, C O; Uyemura, S A et al. (1998) Respiration and oxidative phosphorylation in the apicomplexan parasite Toxoplasma gondii. J Biol Chem 273:31040-7 |
| Zhong, L; Lu, H G; Moreno, S N et al. (1998) Tyrosine phosphate hydrolysis of host proteins by Trypanosoma cruzi is linked to cell invasion. FEMS Microbiol Lett 161:15-20 |
