The ability of typanosomes to grow and multiply in the bloodstream of a mammalian host relies on a complex set of interactions between the parasite and its environment (plasma proteins). Among the African trypanosomes, T. brucei is rapidly lysed by serum (or plasma) from a non-permissive host, such as humans or baboons. Although the nature of the initial lesion remains unclear, it appears that acute, irreversible changes in the permeability properties of the cellular plasma membrane results in colloid osmotic lysis of the cell. Slender trypanosomes of a pleomorphic strain are relatively more sensitive to serum-mediated lysis than stumpy forms. Because the lipid content of slender and stumpy forms differ and because phospholipids can modulate the activity of the serum trypanocidal factor in vitro, it becomes important to understand in more detail the relationship between host and parasite lipid metabolism. The proposed research is based on the hypothesis that the lipid composition of the trypanosome plasma membrane and/or trypanosome lipid metabolism may be important in determining the cell's sensitivity or resistance to the serum trypanocidal factor. The objectives will be a) to isolate and characterize purified plasma membrane fractions of trypanosomes, b) to compare the lipid composition of plasma membranes from sensitive (slender) and resistant (stumpy) trypanosomes, c) to analyze the incorporation of radioactive phospholipid precursors into plasma membrane phospholipids, d) to characterize membrane-associated phospholipases, and e) to compare the phospholipid metabolism of trypanosomes during incubation in control, non-cytotoxic serum from permissive hosts and cytotoxic serum from non-permissive hosts. Elucidation of the biochemical and cellular basis for the specific interaction of trypanocidal plasma proteins with trypanosomes will contribute to a better understanding of those factors which may mediate host range specificity of trypanosomes of the brucei-subgroup. In addition, this research may also point to an important metabolic relationship between these parasites and their host which might be exploited in devising a rational approach to chemotherapy of trypanosomiasis.
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