Shiga Toxin-Producing Escherichia Coli (STEC): the Bug in Our Backyard (Commentary‪)‬

Escherichia coli is one of the members of the family Enterobacteriaceae, which resides as normal gut microflora in humans and other animals. Certain subsets of this species have acquired virulence genes that enable them to cause diarrhoeal and other extraintestinal diseases. Based on the nature of the virulence gene(s) and mechanism(s) by which these cause disease, E. coli isolates have been categorized into different pathotypes (1). One of these pathotypes, enterohaemorrhagic E. coli (EHEC) causes haemorrhagic colitis and haemolytic uraemic syndrome (HUS). HUS occurs mainly in children with triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute renal failure. EHEC constitutes a subset of serotypes called Shiga toxin (Stx)-producing E. coli (STEC), in which Stx is a sine qua non of virulence. The Stx family contains two types, the Stx 1 and Stx2. Stx 1 (Stx 1 and Stx 1c) is antigenically similar to Shiga enterotoxin produced by Shigella dysenteriae type 1. Stx2 is heterogeneous (Stx2c, Stx2d, Stx2e and Stx2f) and immunologically different from Stxl. Both the Stxs have an A-B structure: the A subunit has N-glycosidase activity and the B subunit binds to a membrane glycolipid, globotriaosylceramide (Gb3). Stx is a potent cytotoxin that inhibits protein synthesis within eukaryotic cells. The cytotoxic effect is specific for Vero cell line and hence Stx is also known as verocytotoxin (VT). Epidemiologically, Stx2 seems to be more important in development of HUS. The infective dose of STEC is very low and the pathogenesis is very complex. After ingestion of contaminated food/water, STEC colonizes enterocytes of the large bowel with a characteristic attaching and effacing pathology via components of type III secretion system (TTSS) encoded in the locus of enterocyte effacement (LEE) pathogenicity island. The expression of Stxs is critical for the development of vascular lesions in the colon, kidneys, and central nervous system. Stxs are translocated from the bowel to the circulatory system and transported by leukocytes to capillary endothelial cells in renal glomeruli and other organs. After binding to the receptor globotriaosylceramide on target cells, the toxin is internalized by receptor-mediated endocytosis and interacts with the subcellular machinery to inhibit the protein synthesis. Following routing of Stxs to the endoplasmic reticulum and nuclear membrane, the toxins translocate into the cytoplasm and target ribosomes for damage. These pathophysiological changes result in HUS. The action of Stxs is not limited to inhibition of protein synthesis. Under in vitro conditions, Stx induces macrophages to express tumour necrosis factor alpha, interleukin-1 beta and interleuking. These cytokines and lipopolysaccharide are also reported to increase the susceptibility of cells, which leads to Stx-mediated apoptosis (2).