Pathogenic mechanisms of (a) Shigella flexneri and (b) Yersinia enterocolitica. (a) Shigella interacts preferentially with M cells in the colonic and rectal epithelia (upper panel), activates its T3SS and secretes IpaB and IpaC to form a pore inserted into the host cell membrane (lower panel). The bacterium then delivers effector proteins through the translocon to the eukaryotic cell cytoplasm. IpaC also activates RhoGTPases that, together with activated Src, recruit cortactin, involved in actin filament reorganization. VirA promotes microtubule destabilization, leading to activation of RhoGTPases. IpgD generates PI(5)P, thus promoting cell survival through Akt. IpaA binds to vinculin and induces actin depolymerization. Once inside the host cell, Shigella leaves the vacuole for the cytoplasm and escapes to neighboring cells (upper panel). (b) Yersinia adheres initially to M cells (upper panel) by means of its adhesins: invasin, which binds β₁ integrins directly; and YadA, which binds β₁ integrins indirectly through fibronectin (lower panel). The interactions between the adhesins and integrins cause bacterial internalization following activation of FAK, Rac-1 and Src, which are involved in subtle actin cytoskeletal rearrangements. The vacuole containing the bacterium is transported towards the basolateral side of the M cell, where it is expelled into the dome region of the FAE (upper panel). When Yersinia interacts with phagocyte integrins, the T3SS is activated and a set of effector proteins (Yops) are translocated into the phagocyte cytoplasm. Yops are involved in the antiphagocytic and anti-inflammatory mechanisms used by Yersinia that lead to the formation of microabcesses in the FAE.

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).