Pathogenesis of Shiga-toxin producing escherichia coli

Abstract

Shiga toxin (Stx)-producing Escherichia coli (STEC) are food-borne pathogens that cause hemorrhagic colitis and a serious sequela, the hemolytic uremic syndrome (HUS). The largest outbreaks of STEC are due to a single E. coli serotype, O157:H7, although non-O157 serotypes also cause the same diseases. Two immunologically distinct Stxs are found in E. coli, Stx1 and Stx2. The Stxs are AB₅ toxins that halt protein synthesis in the host cell, a process that may lead to an apoptotic cell death. Stx-mediated damage to renal glomerular endothelial cells is hypothesized as the precipitating event for HUS. A subset of STEC referred to as the enterohemorrhagic E. coli has the capacity to intimately attach to and efface intestinal epithelial cells, a pathology called the A/E lesion. The A/E lesion is mediated by the adhesin intimin, its bacterially encoded receptor, Tir, and effectors secreted through a type III secretion system. The proteins needed for the A/E lesion are encoded within a large pathogenicity island called the locus of enterocyte effacement or LEE. There are several animal models for STEC infection, but no one model fully represents the spectrum of STEC illness. Currently there is no cure for STEC infection, and therapies are based mainly on alleviating symptoms. However, chimeric or humanized monoclonal antibodies have been developed that neutralize the Stxs, and those therapies may be able to prevent the development of HUS in an STEC-infected patient.