Rho/Ras-GTPase-dependent and -independent activity of clostridial glucosylating toxins.

Clostridial glucosylating toxins are the main virulence factors of clostridia responsible for gangrene and/or colitis. These toxins have been well characterized to inactivate Rho/Ras-GTPases through glucosylation. However, the signalling pathways downstream of Rho/Ras-GTPases leading to the intracellular effects of these toxins are only partially known. Rac-dependent modification of focal adhesion complexes and phosphoinositide metabolism seem to be key processes involved in actin filament depolymerization and disorganization of intercellular junctions. In addition, clostridial glucosylating toxins induce Rho/Ras-independent intracellular effects such as activation of mitogen-activated protein kinase pathways, which are used by some of these toxins to trigger an inflammatory response.