Pathogenesis of disease caused by Shigella dysenteriae and Escherichia coli

Abstract

A number of virulence factors are known to be important in disease causation by these enteric bacteria. Proteins expressed by these bacteria regulate invasiveness and allow penetration of the bacterium into the enterocyte and into the adventitia (enteroinvasiveness) with production of typical symptoms and signs of disease. <i>Sh.dyenteriae</i> is internalized via bacterium-directed phagocytosis; polymerization of host cell actin filaments is also bacterially encoded. Other genes (invasion plasmid antigens: IpaA, IpaB, IpaC, IpaD, etc.) encode invasins through plasmid DNA, Virulence genes (VirB, VirG, VirF), are encoded also by a large plasmid. The gene products are produced in defined amounts at critical times in the infection cycle in response to environmental signals such as temperature, osmolality, etc. Cell wall lipopolysaccharide (O-antigen) is needed for intercellular spread and protection against epithelial cell defenses. Enteroinvasive <i>E.coli</i> (EIEC) use shigella-like mechanisms to invade enterocytes. Shiga toxin produced by <i>Sh. dysenteriae</i> 1 is a ribosome poison. Enterohaemorrhagic <i>E.coli</i> (EHEC) utilise Shiga-like toxins I, II, and variants of these toxins to induce disease. Not only are these toxins a major mechanism for production of bloody diarrhoea, but they are responsible for severe forms of toxaemic systemic disease including haemolytic uraemic syndrome (HUS) (mainly SLT-II mediated), and thrombotic thrombocytopenic purpura (TTP) through perturbation of endothelial cell and platelet function. SLT-I and SLT-II are encoded in DNA of bacteriophages and become incorporated into the genome of a restricted number of <i>E. coli</i> OH serotypes. <i>E. coli</i> O157:H7 is responsible for ≈ 50% of cases of HUS in the Northern Hemisphere but is still uncommon in Australia where a wide variety of serotypes are associated with HUS, but <i>E. coli</i> O111:H- seems to be common. Glycosphingolipid (ceramide) receptors for B subunits of SLTs (Gb₃ and Ga₂ on endothelial cells, and erythrocyte P₁ antigen) probably play a role in pathogenesis of HUS and TTP. Enterotoxigenic <i>E.coli</i> (ETEC), cause disease through production of either or both heat stable toxin(s) (ST) or heat labile toxin(s) (LT). Enteropathogenic (EPEC) cause diarrhoea via non-toxigenic mechanisms.