Figure 1

Pathogenic mechanisms of (a) enteropathogenic E . coli (EPEC) and (b) Salmonella enterica. (a) EPEC contact gut epithelial cells, produce BFP (upper panel), and activate their T3SS (lower panel). The bacterium translocates the receptor for its adhesin, intimin, called Tir, through the T3SS into the host cell cytoplasm; the interaction between intimin and Tir promotes tight adhesion. After being phosphorylated by host kinases, the Tir binds Nck, which activates N-WASP, which in turn activates Arp2/3, leading to actin nucleation and formation of a pedestal beneath the bacterium. (b) Salmonella interacts with M cells (upper panel), activates its T3SS and translocates SipA and SipC. SipC localizes to the plasma membrane, where it aids in the translocation of other Salmonella effectors and initiates actin nucleation. The C-terminal domain nucleates actin and the N-terminal domain of SipC bundles it, anchoring the resulting actin filaments to the cell surface below the bacterium. The injected SipA acts in synergy with SipC, as SipA binds to and stabilizes the F-actin filaments, and blocks the action of ADF/cofilin (lower panel). SopE1, SopE2 and SopB activate the RhoGTPases that regulate actin polymerization; SopE1 and SopE2 do so directly by acting as GEFs, and SopB indirectly by interfering with inositol phosphate metabolism. The activated RhoGTPases induce cytoskeletal rearrangements that result in bacterial uptake. SptP then switches off the RhoGTPases, and the eukaryotic cell regains its normal shape. Salmonella replicates inside the vacuole (upper panel).