View the Current Issue

Article

  • The EMBO Journal (2005) 24, 2827 - 2838
  • doi:10.1038/sj.emboj.7600750

Published online: 14 July 2005

Gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein

Didier Cabanes1,a, Sandra Sousa1,a, Antonio Cebriá2, Marc Lecuit1, Francisco García-del Portillo2 and Pascale Cossart1

  1. Unité des Interactions Bactéries Cellules Institut Pasteur, INSERM U604, INRA USC 2020, Paris, France
  2. Departamento de Biotecnologia Microbiana, Centro National de Biotecnologia-CSIC Darwin 3, Madrid, Spain

Correspondence to:

Pascale Cossart, Unité des Interactions Bactéries Cellules Institut Pasteur, INSERM U604, INRA USC 2020, 28 rue du Dr Roux, 75015 Paris, France. Tel.: +33 1 4568 8841; Fax: +33 1 4568 8706; E-mail: pcossart@pasteur.fr

aPresent address: Molecular Microbiology Group, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre, 4150-180 Porto, Portugal

Received 10 February 2005; Accepted 27 June 2005

By comparative genomics, we have identified a gene of the intracellular pathogen Listeria monocytogenes that encodes an LPXTG surface protein absent from nonpathogenic Listeria species. This gene, vip, is positively regulated by PrfA, the transcriptional activator of the major Listeria virulence factors. Vip is anchored to the Listeria cell wall by sortase A and is required for entry into some mammalian cells. Using a ligand overlay approach, we identified a cellular receptor for Vip, the endoplasmic reticulum (ER) resident chaperone Gp96 recently shown to interact with TLRs. The Vip–Gp96 interaction is critical for bacterial entry into some cells. Comparative infection studies using oral and intravenous inoculation of nontransgenic and transgenic mice expressing human E-cadherin demonstrated a role for Vip in Listeria virulence, not only at the intestine level but also in late stages of the infectious process. Vip thus appears as a new virulence factor exploiting Gp96 as a receptor for cell invasion and/or signalling events that may interfere with the host immune response in the course of the infection.

  • Keywords:

    • genomics,
    • Gram positive,
    • GRP94,
    • invasion,
    • pathogen