Caister Academic Press

Receptor Related Risk Factors for Verotoxin Pathogenesis

Clifford Lingwood
from: Bacterial Toxins: Genetics, Cellular Biology and Practical Applications (Edited by: Thomas Proft). Caister Academic Press, U.K. (2013)


The family of E. coli derived verotoxins (Shiga toxins) has been extensively studied over the last 25 years due to its primary role in the infectious etiology of Hemolytic Uremic Syndrome (HUS). This acute pediatric renal disease, defined by the triad of thrombocytopenia, glomerular endothelial damage and hemolytic anemia is mediated by toxin B subunit pentamer binding to its receptor glycosphingolipid, globotriaosyl ceramide (Gb3) within lipid rafts in the glomerular endothelial cell plasma membrane and the subsequent endothelial pathology. HUS is preceded by a self-limiting hemorrhagic colitis prodrome which develops into a systemic pathology in ~10% of patients, after a several days of apparent recovery. Symptoms remain fatal in ~10% of HUS cases and no specific effective interventive therapy has yet been devised. Understanding of the molecular basis and risk factors for HUS following gastrointestinal infection with VT producing E coli, although incomplete and still a matter of controversy, has suffered a severe setback with the most recent highly virulent O104:H4 outbreak which showed more frequent incidence of HUS and death and preferentially targeted the adult female as opposed to the pediatric/elderly population. Since the toxin involved, VT2, was the same as involved in other more typical HUS cases, new concepts to explain this variation in VT-induced pathology are required read more ...
Access full text
Related articles ...