| Enterohemorrhagic Escherichia coli (EHEC) O157:H7, an emerging pathogen, causes severe hemorrhagic colitis and the life-threatening extraintestinal complication of hemolytic uremic syndrome (HUS) in 5 to 10% of patients. EHEC O157:H7, produce Shiga like toxin 1 or 2 (Stx1 or Stx2, respectively), or both. The source of EHEC O157:H7 is mainly of contaminated food or drinking water. Treatment of infection with EHEC O157:H7 has been difficult because antibiotics do not change the course of the enteritis of EHEC O157:H7 and may increase the incidence of HUS caused by the pathogen. This untoward effect has been proposed to be mediated by antibiotic-induced bacteriolysis and release of intracellular Shiga like toxins.Stxs consist of an A-subunit monomer and a B-subunit pentamer. The A subunit's N-glycosidase activity is activated, resulting in the removal of the adenine group from position 4324 in the eukaryotic 28S rRNA of the 60S ribosomal subunit. The resulting A subunit-mediated inhibition of protein biosynthesisis cytotoxic to the target cell. The B subunit is involved in binding to target cells via its glycolipid receptor, globotriaosylceramide (Gb3-Cer). Stxs can be broadly divided into two groups, Stx1 and Stx2. Stx1 and Stx2 fail to cross neutralize and show differences in biological activities in vitro and in vivo. Since Stx2, but not Stx1, is thought to be a major cause of toxity that induces HUS in humans based on epidemiological analyses and studies on EHEC-infected animals.Currently there is no effective treatment or prophylaxis for HUS. As in many toxin-mediated diseases, such as tetanus and botulism, little endogenous serum antibody against Stx is induced following EHEC infection. Nonetheless, passively immune therapy with Stx2-neutralizing antibodies should be very useful in preventing the development of HUS in EHEC infections.Thus a specific therapeutic approach is needed for the prevention of severe disease caused by EHEC infections.
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