Purified verotoxins of Escherichia coli O157:H7 decrease prostacyclin synthesis by endothelial cells.

Two immunologically distinct verotoxins purified from Escherichia coli C600, lysogenized with distinct temperate phages from E. coli strain 933 of serotype O157:H7, were compared by SDS-PAGE and different biological assays. The two toxins termed verotoxin 1 (VT1) and verotoxin 2 (VT2) differing in molecular weight exhibited similar biological activities. Both preparations were toxic for HeLa cells and lethal for mice. Epidemiological evidence of verotoxinogenesis in some cases of hemolytic-uremic syndrome (HUS) and the recent observations of inadequate prostacyclin production by endothelial cells associated with HUS prompted us to study the effect of purified verotoxins on prostacyclin synthesis in rat aortic tissue. Our results demonstrate a significant reduction of prostacyclin by both toxins at picomolar levels. The suppression of prostacyclin release by a lower concentration of VT2 as compared with VT1 reflects the relative potencies of these toxins in HeLa cell toxicity and mouse lethality. The results suggest an effect of verotoxins on endothelial cells and support the concept of these toxins as virulence factors in E. coli.

Hemolytic-uremic syndrome associated with an infection by verotoxin producing Escherichia coli 0111 in a woman on oral contraceptives.

A case of hemolytic-uremic syndrome (HUS) associated with an infection by a verotoxin-producing Escherichia coli (VTEC), serotype 0111:NM, in a 22-year-old woman who had been on oral contraceptives is presented. VTEC-associated cases of HUS infected by E. coli 0111 have been reported before, but never in adults. The kinetics of the humoral immune response to verotoxin in the patient is observed over three months and described for the first time. The possible role of contraceptives that have been incriminated in the etiology of HUS before is discussed as well. Possible benefits of therapeutical interventions such as hemodialysis, therapeutic plasma exchange, converting enzyme inhibitors, or antibiotics still need clarification. However, it is strongly suggested to include tests for VTEC in the work-up of patients suffering from HUS.

PIP: Confirmation of a causal relationship between hemolytic-uremic syndrome (HUS) and verotoxin-producing Escherichia coli (VTEC) infection is provided by the case of a 22-year-old West German woman. The patient presented with fatigue, nausea, and headache. Ultrasonography revealed enlarged kidneys, and laboratory investigations showed uremia, hemolytic anemia, lactate dehydrogenase, haptoglobin below the detection limit, and thrombocytopenia. She received hemodialysis and drug treatment (heparin, dopamine, and furosemide). To investigate the kinetics of the humoral response to verotoxin, the patient was followed for 3 months. Fecal specimens on day 23 yielded E coli serotype 0111:NM, and stool filtrates on days 16 and 23 showed highly cytotoxic activity for HeLa cells. While the patient's initial serum showed a high IgM immune response against purified Shiga toxin, there was a steady decline in IgM and steady increase in IgG antibodies over the ensuing 3 months. These findings are suggestive of a recent infection by a verotoxin-producing organism. This is the 1st reported case of VTEC-associated HUS with e coli 0111 infection in an adult, and the patient's 4-year history of oral contraceptives (OCs)--ethinyl estradiol and chlormadinoneacetate--is considered to be of etiologic significance. The diminished antibody coating of bacteria in the urinary tract of OC users may have facilitated invasion of verotoxin across the mucosal barrier in this patient. Severe hypertension has been reported previously in OC users with HUS. It is speculated that verotoxin may trigger HUS in longterm OC users, initiating vasoconstriction and microangiopathic hemolysis.