Cellular and bacterial factors involved in modulation of the actin dynamics following infection with enteropathogenic and enterohemorrhagic E. coli

Enteropathogenic (EPEC) and enterohaemorrhagic E. coli (EHEC) are extracellular human pathogens, EHEC O157:H7 is the most virulent serotype but other, non-O157, strains are emerging. EPEC and EHEC use a type III secretion system to translocate the Tir protein into the plasma membrane of the host cell. Through interaction with the outer membrane adhesion molecule intimin, Tir connects the extracellular bacterium to the host cell actin cytoskeleton. Intimin-Tir interaction focuses Tir and triggers actin polymerization at the site of bacterial adhesion. While both converge on N-WASP, Tir-mediated actin accretion by EPECE2348/69 requires Tir tyrosine (TirY474) phosphorylation and the host adaptor Nck, whereas TirEHEC is not phosphorylated and utilizes TccP, a bacterial effector that binds, albeit indirectly, Tir and activates N-WASP. While screening for TccP among a large collection of EPEC and non-O157 EHEC, we found that many strains carry TccP and a TirY474 equivalent. Preliminary results showed that the TccP/TirY474 strains simultaneously utilize the Nck and TccP pathways during infection, defining a new class of versatile and potentially more virulent diarrhoeagenic E. coli.