|
|
|
|
|
|
|
|
|
|
|
|
|
From left to right : Back : Boris Foultier - Noureddine Rhazi - Paul Troisfontaines - Guy R. Cornelis- Marie-Noelle Marenne - Rachid Benabdillah Middle : Marie Monteforte - Isabelle Lambermont - Marie-Eve Renard - Simone Mueller - Nadine Grosdent Front : Mario Feldman - Dominique Desnoeck - Nathalie Sauvonnet - Geertrui Denecker |
The microbial pathogenesis unit is studying the Yop virulon, a sophisticated pathogenicity system used by bacteria from the genus Yersinia (Y. enterocolitica , Y. pseudotuberculosis and Y. pestis) to defeat the immune system of their host . For reviews see Cornelis, G.R. J.Bacteriol. 180: 5495-5504 (short) and Cornelis G.R. et al. Microbiology and Molecular Biology Reviews (ASM), 1998, 62:1315-1352 (extensive). This system allows extracellular bacteria adhering at the surface of eukaryotic cells to inject bacterial effector proteins into the cytosol of these cells (Sory and Cornelis, Mol. Microbiol. 14:583-594, 1994), which disarms them or sabotages their communications (Figure 1). This system is the archetype of a whole family of systems (called "type III systems") encountered in several animal and plant pathogens. In Y. enterocolitica, it is encoded by a 70-kb plasmid that is completely sequenced (Iriarte et al., GenBank AF102990, 1999).
In Yersinia, the known effectors are YopE, YopH, YopO (also called YpkA), YopP (also called YopJ), YopM and YopT (Iriarte and Cornelis, Mol. Microbiol. 29: 915-929, 1998). YopE and YopT are cytotoxins that lead to the disruption of actin filaments, YopH is a phosphotyrosine phosphatase acting on two kinases of the focal adhesion plaque while YopO is a serine-threonine kinase. After injection into the macrophage, YopH and YopE inhibit phagocytosis while YopP prevents the release of the proinflammatory cytokine TNFa (Boland and Cornelis, Infect. Immun. 1998) and induces apoptosis (Mills et al, PNAS 94:789-797,1997).
Delivery of the Yop effectors requires the 25 YscA-Y proteins, YopB, YopD, LcrV and LcrG, which are encoded by four contiguous operons. The Ysc proteins allow the Yops to cross the two bacterial membranes (Michiels et al., Infect. Immun. 58:2840-49,1990). YopB, YopD, LcrV and LcrG are required to transfer the effector Yops across the eukaryotic cell membrane. How they are associated to the Ysc apparatus is still not known.
Secretion of the Yops and deployment of YopB, YopD and LcrV at the bacterial surface is triggered by contact with eukaryotic cells and controlled by proteins of the virulon including YopN, which is supposed to act as a stop-valve closing the bacterial secretion channel (Boland et al., EMBO J. 15: 5191-5201, 1996).
The proper operation of the system also requires the presence in the bacterial cytosol, of small individual chaperones, called the Syc proteins (Wattiau and Cornelis, Mol. Microbiol. 8:123-131; Wattiau et al., PNAS 91: 10493-10497, 1994). Five such chaperones have been described so far: SycE for YopE, SycH for YopH, SycN for YopN, SycT for YopT and finally SycD for YopB and YopD (Neyt and Cornelis, Mol. Microbiol. 31: 143-156).
Figure 1: the basic model.
When yersinia are placed at 37 ƒC in a rich environment, the Ysc secretion apparatus is installed and a stock of Yop proteins is synthesized. As long as there is no contact with a eukaryotic cell, a stop-valve, possibly made of YopN, TyeA and LcrG, blocks the Ysc secretion channel. Upon contact with the eukaryotic target cell a sensor interacts with a receptor on the cell surface which results in the opening of the secretion channel at the zone of contact. The Yops are then transported through the secretion channels and the Yop effectors are translocated across the plasma membrane guided by YopB and YopD. During their intrabacterial stage, Yops are capped with their specific Syc chaperone, presumably to prevent premature associations.
Tél: 02/764.74.49
Fax: 02/764.74.98
Page : UCL | ICP | Pointeurs utiles.
