Verotoxin biology: molecular events in vascular endothelial injury

Escherichia coli-derived verotoxins (VTs) play a critical role in the pathogenesis of hemolytic uremic syndrome (HUS) in major part due to vascular endothelial damage. Perturbations in endothelial phenotype account for many of the clinical features observed in patients. VTs inactivate host cell ribosomes and prevent protein synthesis. Interestingly, however, they also dramatically alter gene expression at concentrations that have only minor effects on overall mRNA translation. Using endothelin-1 as a model, we describe the molecular mechanisms by which VT alters the endothelial cell phenotype in HUS. RNA metabolism pathways and effects on translation may play central roles in the molecular events operative in vascular injury mediated by these potent bacteria-derived exotoxins.