OLIGOPEPTIDASE B-DEPENDENT SIGNALING MEDIATES HOST-CELL INVASION BY TRYPANOSOMA-CRUZI

Mammalian cell invasion by the intracellular protozoan parasite Trypan osoma cruzi is mediated by recruitment and fusion of host cell lysosom es, an unusual process that has been proposed to be dependent on the a bility of parasites to trigger intracellular free calcium concentratio n ([Ca2+](i)) transients in host cells. Previous work implicated the T .cruzi serine hydrolase oligopeptidase B in the generation of Ca2+-sig naling activity in parasite extracts. Here we show that deletion of th e gene encoding oligopeptidase B results in a marked defect in host ce ll invasion and in the establishment of infections in mice, The invasi on defect is associated with the inability of oligopeptidase B null mu tant trypomastigotes to mobilize Ca2+ from thapsigargin-sensitive stor es in mammalian cells. Exogenous recombinant oligopeptidase B reconsti tutes the oligopeptidase B-dependent Ca2+ signaling activity in null m utant parasite extracts, demonstrating that this enzyme is responsible for the generation of a signaling agonist for mammalian cells.