Gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein.
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.
Cabanes
Didier
D
Unité des Interactions Bactéries Cellules Institut Pasteur, INSERM U604, INRA USC 2020, Paris, France.
Sousa
Sandra
S
Cebriá
Antonio
A
Lecuit
Marc
M
García-del Portillo
Francisco
F
Cossart
Pascale
P
D000217:Acyltransferases / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000378:metabolism*; D018938:Caco-2 Cells; D003546:Cysteine Endopeptidases; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism* / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
D000951:Antigens, Neoplasm; D001426:Bacterial Proteins; D008565:Membrane Proteins; D010454:Peptide Termination Factors; D015534:Trans-Activators; C503594:Vip protein, Listeria monocytogenes; D037521:Virulence Factors; C052646:sarcoma glycoprotein gp96 rejection antigens; D000217:Acyltransferases; C118473:LpxL protein, bacteria; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases