The cell biology and biochemistry of Leishmania and Trypanosoma are investigated as models of intra- and extracellular parasitism, respectively. As all interactions between host and parasite occur at the level of the parasite surface membrane (SM), emphasis is placed on: 1) its integrated biochemical characterization and 2) defining its roles in parasite survival. Using Western blots, the major SM antigens of L. donovani to which visceral leishmaniasis patients make IgG responses were identified. The glycolipid constitutents of L. donovani promastigote SM were delineated. A secreted promastigote acid phosphatase was purified, chemically characterized and monoclonal antibodies raised against it. Amastigotes also release this enzyme and visceral patients make IgG antibodies against it. Log-phase promastigotes were shown to activate and be killed by the alternate complement pathway and the primary target of C3-binding was identified as a SM protein of 140 Kd. An active transport system for ribose was demonstrated and characterized in L. donovani promastigotes. Regulation of SM 3'-nucleotidase activity was shown to be under inducible genetic control. A SM proton-ATPase which drives membrane transport processes was identified, cytochemically localized and enzymatically characterized. The SM glucose transport protein of promastigotes was identified via photoaffinity labeling and partially characterized. Genomic clones coding for parasite SM antigens were identified, isolated and characterized from an expression-vector system using both anti-SM sera and sera from visceral leishmaniasis patients.
Showing the most recent 10 out of 26 publications
