Figure 10.

A presumed model for the action of EPEC type III effectors in host cells. EPEC injects the effectors (e.g., Tir, EspF, EspG, and the EspG homolog Orf3) via a type III secretion machinery into the host cells. The interaction of a bacterial membrane protein, intimin, and translocated Tir triggers the host signal transduction pathway, which includes the recruitment of Nck, N-WASP, and the Arp2/3 complex, resulting in the formation of a pedestal structure beneath the adherent bacteria. On the other hand, it is possible that EspF and EspG/Orf3 influence the function of cell junctions (CJs). Although the precise function of EspF is not clear at present, EspF is known to exert an effect on the morphology of tight junction strands. EspG and Orf3 associate with tubulins, resulting in the disruption of microtubule networks. GEF-H1 switches to the active form as a result of its dissociation from microtubule networks. Activated GEF-H1 promotes the binding of GTP to RhoA, resulting in the activation of RhoA. Finally, the activation of ROCK, which is located downstream of the RhoA signal, induces actin stress fiber assembly and probably exerts influence on paracellular permeability in EPEC-infected cells.