Actin Cytoskeleton Manipulation by Effector Proteins Secreted by Diarrheagenic Escherichia coli Pathotypes
Figure 3
Models of actin cytoskeleton manipulation by enteroaggregative E. coli (EAEC) and diffusely adherent E. coli (DAEC). EAEC secrete to the serine protease autotransporte of Enterobacteriaceae known as Plasmid-encoded toxin (Pet). Pet enters the eukaryotic cell and that trafficking through the vesicular system is required for the induction of cytopathic effects. Thus, after clathrin-mediated endocytosis, Pet undergoes a retrograde trafficking from the Golgi apparatus to the endoplasmic reticulum to be translocated into the cytosol. Where, Pet reaches one of its intracellular target, α-fodrin (αII spectrin). Pet cleaves epithelial fodrin (between M1198 and V1199 residues), causing fodrin redistribution within the cells; fodrin is a structural link between the plasma membrane and the cortical actin cytoskeleton. On the other hand, Afa/Dr DAEC interact with membrane-bound receptors including the recognition of DAF by Afa/Dr adhesins and of CEACAMs. This receptor recognition develops loss of microvilli, which results from a signaling pathway involving protein tyrosine kinase (PKT), phospholipase Cγ, phosphatidylinositol 3-kinase (PLCγ), protein kinase C (PKC), and an increase in . These events control the rearrangements of brush border-associated F-actin and villin cytoskeletal proteins. The elongation of the microvilli also involves the activation of Rho GTPase Cdc42. Secreted autotransporter toxin (Sat) plays an important role in the increased paracellular permeability, which is associated with the reorganization of TJ-associated proteins, ZO-1 and occludin, but does not affect the TER. Internalization occurs in non-polarized epithelial cells via a mechanism involving lipid rafts and dynamic microtubules. Internalized Afa/Dr DAEC bacteria survive within a large, late vacuole (for full details, see main text).
