## 1 Introduction  
It has been only thirty years since Shiga toxin-producing _Escherichia coli_ was recognized as a human pathogen after the first outbreak investigated as hemorrhagic colitis in 47 patients in Oregon and Michigan [1]. This _E. coli_ O157:H7 strain was then considered to be rare, but the 1993 multistate outbreak from undercooked hamburgers at a fast-food chain gained national attention for this newly emerging pathogen [2]. By 2002 there were 350 outbreaks (\(\geq\)2 cases with same exposure source) reported to the CDC in 49 states, sickening 8598 people with a 17.4% hospitalization rate [3]. Contaminated ground beef and fresh produce account for about 75% of the infections, with the remainder being person-to-person, waterborne or animal contact sources and the vast majority (92%) occurring seasonally from May to November [3]. Enterohemorrhagic _E. coli_ (EHEC) are not invasive, so bacteremia is rare, but they secrete ribosome inactivating Shiga-like toxins (Stx1 and Stx2 with variants) which are responsible for much of the organ damage [4,5], and Stx2 is more frequently associated with severe disease. Several recent reviews discuss the molecular basis for bacterial success and toxin biochemistry [6, 7, 8]. Bacterial colonization of the intestine with attaching and effacing lesions support type III secretion of toxins into the vasculature [6]. Micropinocytosis may contribute as toxin antigen is observed in patient gut epithelial cells in the absence of A/E lesions [9]. The very young and the elderly are most susceptible to complications and death from EHEC infection. This bacterial infection is the leading cause of acute kidney failure in otherwise healthy children in the US with an average infection rate of 1/100,000. Children less than five years of age are more likely to develop complications requiring hospitalization and kidney dialysis, and the elderly \(>\)60 years are more likely to die regardless of the clinical complications [10]. This emerging pathogen has become a global problem as well. The 1996 O157:H7 outbreak in thousands in Sakai City, Japan was purportedly from contaminated bean sprouts distributed in elementary school lunches [11]. The summer 2011 outbreak sourced to bean sprouts in Germany left over 4000 infected [12] and sent a clear warning through the EHEC research and clinical infectious disease communities that more virulent strains are emerging. This O104:H4 strain was a combination of an enteroaggregative _E. coli_ strain, normally characterized by intestinal mucosa adherence to cause self-limiting diarrhea [13], that picked up the _stx2_ gene, thereby acquiring high virulence and causing severe clinical consequences, particularly acute kidney injury from hemolytic uremic syndrome and severe neurological abnormalities [14,15]. [PERSON] _et al._ was the first to make the association between Stx, diarrheal _E. coli_ infection and the idiopathic hemolytic uremic syndrome of infancy and childhood [16,17]. This critical link provided the first molecular explanation for the clinical observations, thereby opening new routes for differential diagnosis and pathogen-specific treatment modalities. Hemolytic uremic syndrome (HUS) is a serious clinical complication of EHEC infection and the severity of a public outbreak is often discussed in terms of the HUS rate. HUS is a clinical composite of thrombocytopenia, hemolytic anemia and thrombotic microangiopathy that contributes to acute kidney injury, often requiring dialysis and can progress to acute renal failure and death. Epidemiology studies have shown that HUS typically develops in about 5%-15% of patients, but this varies between bacterial strains and geographic location. Treatment is supportive, no toxin-specific therapies are available and antibiotics are usually contraindicated, depending on serotype.