Schistosomiasis caused by parasitic blood
flukes of the genus Schistosoma is the second most important parasitic
infection after malaria with more than 240 million people infected. There is an
urgent need to identify novel anti-schistosomal targets for therapeutic
interventions. Our work is focused on S. mansoni serine protease
2 (SmSP2). It was localized in the tegument and esophageal glands, ovaries,
testes and vitelaria of adult schistosomes by immunofluorescence microscopy and
in situ RNA hybridization. Enzyme activity measurements and
immunoblotting identified SmSP2 in the excretory/secretory products.
Recombinant SmSP2 was produced in the Pichia pastoris expression system and its
cleavage specificity was investigated using combinatorial substrate libraries
and 3D model analysis. SmSP2 was found to activate plasmin, the key component
of the fibrinolytic system, and releases vasoregulatory kinins from kininogen.
Our results suggest that SmSP2 plays a role in host-parasite interactions and
represents a potential target for novel drug or vaccine interventions.