Shiga Toxin–Producing \u3ci\u3eEscherichia coli\u3c/i\u3e in Montana: Bacterial Genotypes and Clinical Profiles

The diseases and virulence genes associated with Shiga toxin–producing Escherichia coli (STEC) are characterized incompletely. We analyzed, by polymerase chain reaction, 82 STEC isolates collected prospectively in Montana and profiled associated illnesses by patient chart review. All E. coli O157:H7 contained stx2-group genes, as well as eae, iha, espA, and ehxA; 84% contained stx1. Non-O157:H7 STEC less frequently contained stx1( P = .046 ), stx2 (P \u3c .001), iha (P \u3c .001), eae, and espA (P = .039 for both), were isolated less often from patients treated in emergency departments (P = .022), and tended to be associated less frequently with bloody diarrhea (P = .061). There were no significant associations between stx genotype and bloody diarrhea, but isolates containing stx2c or stx2d-activatable were recovered more often from patients who underwent diagnostic or therapeutic procedures (P = .033). Non-O157:H7 STEC are more heterogeneous and cause bloody diarrhea less frequently than do E. coli O157:H7. Bloody diarrhea cannot be attributed simply to the stx genotype of the infecting organism

A novel murine infection model for Shiga toxin-producing Escherichia coli

Enterohemorrhagic E. coli (EHEC) is an important subset of Shiga toxin-producing (Stx-producing) E. coli (STEC), pathogens that have been implicated in outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to intestinal epithelium, EHEC generates attaching and effacing (AE) lesions characterized by intimate attachment and actin rearrangement upon host cell binding. Stx produced in the gut transverses the intestinal epithelium, causing vascular damage that leads to systemic disease. Models of EHEC infection in conventional mice do not manifest key features of disease, such as AE lesions, intestinal damage, and systemic illness. In order to develop an infection model that better reflects the pathogenesis of this subset of STEC, we constructed an Stx-producing strain of Citrobacter rodentium, a murine AE pathogen that otherwise lacks Stx. Mice infected with Stx-producing C. rodentium developed AE lesions on the intestinal epithelium and Stx-dependent intestinal inflammatory damage. Further, the mice experienced lethal infection characterized by histopathological and functional kidney damage. The development of a murine model that encompasses AE lesion formation and Stx-mediated tissue damage will provide a new platform upon which to identify EHEC alterations of host epithelium that contribute to systemic disease

A Case of a Shiga Toxin Producing Escherichia Coli

We encountered a patient with hemolytic uremic syndrome (HUS) with persistent isolation of shiga toxin-producing Escherichia coli (STEC) for 3 weeks despite of having no clinical symptoms. STEC has been recognized as an important food-borne pathogen that causes severe diseases such as HUS. We characterized this STEC strain via a polymerase chain reaction, reverse-passive latex agglutination and the slide agglutination method. In this STEC strain, stx2 (shiga toxin), eaeA, tir, iha (adherence genes), espADB (type III secretion genes), and hlyA, ehxA, clyA (hemolysin genes) were present. The O antigen of the strain was non-typable

All blood, No stool: enterohemorrhagic Escherichia coli O157:H7 infection

Enterohemorrhagic Escherichia coli serotype O157:H7 is a pathotype of diarrheagenic E. coli that produces one or more Shiga toxins, forms a characteristic histopathology described as attaching and effacing lesions, and possesses the large virulence plasmid pO157. The bacterium is recognized worldwide, especially in developed countries, as an emerging food-borne bacterial pathogen, which causes disease in humans and in some animals. Healthy cattle are the principal and natural reservoir of E. coli O157:H7, and most disease outbreaks are, therefore, due to consumption of fecally contaminated bovine foods or dairy products. In this review, we provide a general overview of E. coli O157:H7 infection, especially focusing on the bacterial characteristics rather than on the host responses during infection

AB Toxins: A Paradigm Switch from Deadly to Desirable

To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity

Shiga toxin (Stx) type 2‐induced increase in O‐linked N‐acetyl glucosamine protein modification: a new therapeutic target?

Shiga toxin (Stx)‐producing Escherichia coli (STEC) causes bloody diarrhea, which may progress to the potentially fatal hemolytic uremic syndrome (HUS). Development of HUS after STEC infection is dependent on Stx, and is particularly linked to Stx type 2a, Stx2a (Melton‐Celsa, 2014; Scheutz, 2014). In this issue of EMBO Molecular Medicine, Lee et al report that O‐linked N‐acetyl glucosamine protein modification (O‐GlcNAcylation) is increased in host cells after Stx exposure and the subsequent endoplasmic reticulum (ER) stress response. The elevated O‐GlcNAcylation resulted in elevated inflammatory and apoptotic processes. Inhibition of O‐GlcNAcylation with OSMI‐1 protected cells from the Stx2a‐induced damage. In mice intoxicated with Stx2a, OSMI‐1 treatment reduced kidney damage and increased mouse survival

Activation of Shiga-Like Toxins by Mouse and Human Intestinal Mucus Correlates with Virulence of Enterohemorrhagic \u3ci\u3eEscherichia coli\u3c/i\u3e O91:H21 Isolates in Orally Infected, Streptomycin-Treated Mice

The enterohemorrhagic Escherichia coli (EHEC) O91:H21 isolates B2F1 and H414-36/89 are virulent in an orally infected streptomycin-treated mouse model. Previous studies demonstrated that B2F1 and H414-36/89 grow to high levels in mucus isolated from the mouse small intestine and colon and that growth in smallintestinal mucus is related to virulence. We measured the levels of Shiga-like toxins (SLTs) SLT-IIvha and SLT-IIvhb produced by B2F1 after growth in Luria-Bertani (LB) broth supplemented with mouse intestinal mucus by assaying the cytotoxicity of culture supernatants on Vero cells. Culture supernatants from B2F1 grown in mouse intestinal mucus, but not EHEC strains that produce SLT-II or SLT-IIc, were approximately 35- to 350-fold more toxic for Vero cells than supernatants from B2F1 grown in LB broth. This increased toxicity was not reflected by a concomitant increase in SLT antigen content. Furthermore, when culture supernatants from B2F1 or K-12 strains carrying plasmids encoding SLTs cloned from H414-36/89 or purified SLT-IIvhb from B2F1 were incubated with mouse intestinal mucus, the samples exhibited greater cytotoxicity than when they were incubated with N-2-hydroxyethylpiperazine-N\u27-2-ethanesulfonic acid (HEPES) buffer alone. These toxin preparations also showed increased cytotoxicity after incubation with human colonic mucus. In contrast, culture supernatants from LB-grown EHEC isolates that produced SLT-I, SLT-II, SLT-IIc, or SLT-IIe did not show increased cytotoxicity after incubation with mouse or human intestinal mucus. The A subunits of purified SLT-II and SLT-IIvhb that had been treated with mouse intestinal mucus or trypsin were cleaved to A1 fragments by the mucus, but trypsin-mediated cleavage, unlike treatment with mouse intestinal mucus, did not result in increased Vero cell cytotoxic activity. This finding implies that the increased cytotoxicity of SLT-IIvhb detected after incubation with mucus is probably not due to cleavage of the A subunit into the A1 and A2 fragments. Taken together, these results indicate that mouse or human intestinal mucus directly activates SLT-II-related toxins from B2F1 and H414-36/89 and suggest that toxin activation may explain the low 50% lethal doses of B2F1 and H414-36/89 in streptomycin-treated mice