Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus

Nadine Borchert, Christoph Becker-Pauly, Antje Wagner, Peter Fischer, Walter Stöcker, Norbert W. Brattig

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The tissue-invasive nematode Onchocerca volvulus causes skin and eye pathology in human onchocerciasis. While the adult females reside sessile in subcutaneous nodules, the microfilariae are abundantly released from the nodules, males and juvenile worms migrate through the host tissue. Matrix-degrading metallo- and serine proteinases have been detected in excretory-secretory worm products that may be essential for migration of the mobile stages. In this study, a 1713 bp long cDNA encoding for a putative proteinase of O. volvulus has been isolated. The predicted protein sequence includes a signal peptide indicating secretion to the extracellular space, a propeptide, an astacin-like protease domain, an EGF-like and a CUB-domain, thereby identifying the protein as a member of the astacin family of zinc endopeptidases. Onchoastacin, Ov-AST-1, is most closely related to a subfamily comprising nematode astacins including Caenorhabditis and Ancylostoma. Ov-AST-1 was expressed as a recombinant protein in baculovirus-infected insect cells and exhibited enzymatic activity. The exposure of onchoastacin to the host immune system is indicated by demonstration of IgG reacting with the recombinant Ov-AST-1 and with two peptides of the protein. Since a homologous metalloproteinase is part of a promising hookworm vaccine, Ov-AST-1 may be a candidate for intervention strategies in filarial infections.

Original languageEnglish
Pages (from-to)498-506
Number of pages9
JournalMicrobes and Infection
Volume9
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • Astacin
  • Excretory/secretory products
  • Metalloproteinase
  • Onchocerca
  • filaria

Fingerprint

Dive into the research topics of 'Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus'. Together they form a unique fingerprint.

Cite this