Schistosoma mansoni: expression and role of cysteine proteinases in developing schistosomula.

The adult stage of Schistosoma mansoni utilizes host hemoglobin as a nutrient source. A proteolytic enzyme (SMw32) that has "hemoglobinase" activity is secreted into the parasite gut where it appears to be rapidly activated by glutathione released from host red blood cells. In the present study the expression of this proteinase, in developing schistosomula, has been correlated with digestive tract development and a dramatic rise in enzyme activity as early as Days 8-10 of culture. No evidence of the SMw32 proteinase was found in eggs, cercariae, or in newly transformed larvae. Further, the proteinase expressed at Days 8-10 is indistinguishable from the adult worm enzyme. In the larvae, indirect immunofluorescence with an anti-SMw32 monoclonal antibody showed that the proteinase is found throughout the developing cecum. The importance of cysteine proteinases to parasite development was also studied using a specific enzyme inhibitor, Ep-459. In cultures containing Ep-459 most (75%) of the schistosomula failed to survive the 18-day study period. Moreover, those that did survive showed a decrease in their growth (body length). These data suggest that the SMw32 proteinase is a developmentally regulated enzyme and that cysteine proteinase activity is essential in providing nutrients for the growth and survival of this parasite in its mammalian host. Thus, this proteinase may be an important target for chemotherapeutic intervention.