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

Elisabet V. Caler, Silvia Vaena De Avalos, Paul A. Haynes, Norma W. Andrews*, Barbara A. Burleigh

*Corresponding author for this work

Research output: Contribution to journalArticle

164 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4975-4986
Number of pages12
JournalEMBO Journal
Volume17
Issue number17
DOIs
Publication statusPublished - 1 Sep 1998
Externally publishedYes

Keywords

  • Ca signaling
  • Cell invasion
  • Oligopeptidase B
  • Parasite
  • Trypanosoma cruzi

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