Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi.

Abstract

Mammalian cell invasion by the intracellular protozoan parasite Trypanosoma cruzi is mediated by recruitment and fusion of host cell lysosomes, an unusual process that has been proposed to be dependent on the ability of parasites to trigger intracellular free calcium concentration ([Ca2+]i) transients in host cells. Previous work implicated the T.cruzi serine hydrolase oligopeptidase B in the generation of Ca2+-signaling activity in parasite extracts. Here we show that deletion of the gene encoding oligopeptidase B results in a marked defect in host cell invasion and in the establishment of infections in mice. The invasion defect is associated with the inability of oligopeptidase B null mutant trypomastigotes to mobilize Ca2+ from thapsigargin-sensitive stores in mammalian cells. Exogenous recombinant oligopeptidase B reconstitutes the oligopeptidase B-dependent Ca2+ signaling activity in null mutant parasite extracts, demonstrating that this enzyme is responsible for the generation of a signaling agonist for mammalian cells.

• Authors: E V Caler, S Vaena de Avalos, P A Haynes, N W Andrews, B A Burleigh
• Journal: The EMBO journal (EMBO J) Vol. 17 Issue 17 Pg. 4975-86 (Sep 01 1998) ISSN: 0261-4189 [Print] England
• PMID: 9724634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Protozoan Proteins
• Serine Endopeptidases
• oligopeptidase B

Topics

• Animals
• Calcium Signaling
• Female
• Gene Deletion
• Haplorhini
• HeLa Cells
• Humans
• Mice
• Mice, Inbred C3H
• Models, Biological
• Muscles (cytology, parasitology)
• Mutagenesis
• Protozoan Proteins (metabolism)
• Rats
• Serine Endopeptidases (genetics, metabolism)
• Trypanosoma cruzi (genetics, pathogenicity)