Human Antibody against Shiga Toxin 2 Administered to Piglets after the Onset of Diarrhea Due to
            <i>Escherichia coli</i>
            O157:H7 Prevents Fatal Systemic Complications

Sheoran, Abhineet S.; Chapman-Bonofiglio, Susan; Harvey, Barrett R.; Mukherjee, Jean; Georgiou, George; Donohue‐Rolfe, Arthur; Tzipori, Saul

doi:10.1128/iai.73.8.4607-4613.2005

Cited by 75 publications

(100 citation statements)

References 55 publications

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“…In addition, we observed that the OIA method was more sensitive than the EIA (14). In addition, therapies such as humanized monoclonal antibodies that can be passively administered to protect against Shiga toxins are in development (5,13). Once these therapies are available, at-risk patients who have been identified by rapid toxin detection methods can be treated promptly, since the efficacy of such interventions is likely to be proportional to the speed with which therapy is administered.…”

Section: Discussionmentioning

confidence: 96%

Rapid Detection of Shiga Toxin-Producing Escherichia coli by Optical Immunoassay

et al. 2007

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In a multi-health center study, a new rapid optical immunoassay (OIA) for the detection of Shiga toxin types 1 and 2, the BioStar OIA SHIGATOX kit (Inverness Medical Professional Diagnostics, Inc.), was used to prospectively screen 742 fresh fecal samples for Shiga toxins in parallel with the Premier enterohemorrhagic Escherichia coli (EHEC) kit (Meridian BioScience, Inc.) with and without enrichment of the specimens by incubation in MacConkey broth. Additionally, 85 previously tested frozen fecal samples were assessed as described above. All positive immunoassay results were confirmed by the Vero cell cytotoxicity assay. A further modification of the screening procedure was evaluated on 470 of the prospectively screened specimens. Swabs of growth from conventionally plated stool culture media were subjected to the OIA SHIGATOX, and results were compared with those obtained with the Premier EHEC kit following broth enrichment. Overall, the OIA SHIGATOX kit was significantly more sensitive than the Premier EHEC kit on fresh direct stool specimens (sensitivities, 96.8% and 83.9%, respectively; P < 0.05). The two assays performed equally well with each other on frozen and broth-enriched samples. The colony sweep method used in conjunction with the OIA kit was somewhat more effective at detection of Shiga toxins from growth on agar than the overnight broth enrichment procedure used with the Premier EHEC assay (sensitivities, 100% and 92%, respectively; P < 0.09). Overall, the OIA SHIGATOX kit provided rapid, easy-to-interpret results and was highly effective at detection of Shiga toxin-producing E. coli in fecal samples and overnight cultures.

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Section: Discussionmentioning

confidence: 96%

Rapid Detection of Shiga Toxin-Producing Escherichia coli by Optical Immunoassay

et al. 2007

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“…In this contribution different approaches have aimed to neutralize Stx by the use of pharmacological compounds (26), specific antibodies (27,28), or recombinant bacteria expressing globotriaosylceramide-3 (29). Herein, we present NO, a critical mediator of the host mucosal innate immune response, as a potent inhibitor of Stx2 synthesis by EHEC.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli

Vareille¹,

Sablet²,

Hindré³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Shiga-toxin (Stx) is the cardinal virulence factor of enterohemorrhagic Escherichia coli (EHEC). The genes encoding Stx are carried by a lambdoid phage integrated in the bacterial genome and are fully expressed after a bacterial SOS response induced by DNAdamaging agents. Because nitric oxide (NO) is an essential mediator of the innate immune response of infected colonic mucosa, we aimed to determine its role in Stx production by EHEC. Here we demonstrate that chemical or cellular sources of NO inhibit spontaneous and mitomycin C-induced stx mRNA expression and Stx synthesis, without altering EHEC viability. The synthesis of stx phage is also reduced by NO. This inhibitory effect apparently occurs through the NO-mediated sensitization of EHEC because mutation of the NO sensor nitrite-sensitive repressor results in loss of NO inhibiting activity on stx expression. Thus our findings identify NO as an inhibitor of stx expressing-phage propagation and Stx release and thus as a potential protective factor limiting the development of hemolytic syndromes.bacterial infection ͉ mucosal immunology E nterohemorrhagic Escherichia coli (EHEC) are pathogens carried by healthy rearing animals. After infection through the ingestion of contaminated food, EHEC colonize the large intestine and cause gastrointestinal diseases ranging from uncomplicated diarrhea to hemorrhagic colitis. Life-threatening complications, such as hemolytic-uremic syndrome (HUS), develop in Ϸ5-10% of EHEC-infected patients. HUS is defined by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, which can yield to a chronic renal failure and even death (1-3). O157:H7 is the main EHEC serotype implicated in HUS in Europe and North America (3). The few recent large outbreaks (4, 5) underline that prevention of primary infection in human remains an elusive goal. Therefore, understanding host-EHEC interactions remains a critical issue in fighting bacterial infection and HUS development.The main EHEC virulence factor associated with severe human diseases is the Shiga toxin (Stx). Both Stx1 and Stx2 are heteropolymers constituted by a catalytic A subunit and five B subunits implicated in the binding to the receptor glycolipid globotriaosylceramide-3 of endothelial cells. Internalized Stx alters ribosomal function and induces the death of vascular cells (1, 3). Stx1 and Stx2 are encoded by two type lysogenic phages integrated in the bacterial genome (6). In a lysogen, the expression of the phage operons is controlled by the protein CI. As a result of EHEC exposure to DNA-damaging agents such as mitomycin C (7) or H 2 O 2 (8), RecA, which is part of the so-called SOS response, is activated by single-strand DNA and promotes the autocleavage of CI (9). Then, a regulatory cascade yields to the respective expression of the genes encoding the antiterminators N and Q, Stx, and proteins of phage morphogenesis and lysis (9-13). Bacteria are lysed and release Stx and free phage particles in the medium.An important hallmark of EHEC pathoge...

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“…Research in this field is still ongoing, but to date, the results have been disappointing [111] . Another option for the future is to treat patients during the diarrheal phase with monoclonal antibodies against Shiga toxin [112] . In December 2005, the United States Food and Drug Administration (FDA) approved orphan drug status for 2 chimerical anti-Stx antibodies.…”

Section: Peculiar Consideration For Treatment Of Hus D+mentioning

confidence: 99%

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Salvadori

Bertoni²

2013

WJN

112

111

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Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both "traditional therapy" (including plasma therapy, kidney and kidneyliver transplantation) and "new therapies". The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody "eculizumab". Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.

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Human Antibody against Shiga Toxin 2 Administered to Piglets after the Onset of Diarrhea Due to Escherichia coli O157:H7 Prevents Fatal Systemic Complications

Cited by 75 publications

References 55 publications

Rapid Detection of Shiga Toxin-Producing Escherichia coli by Optical Immunoassay

Rapid Detection of Shiga Toxin-Producing Escherichia coli by Optical Immunoassay

Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

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