Abstract
BackgroundHemolytic uremic syndrome (HUS) is a systemic and potentially fatal complication of gastroenteritis secondary to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infection characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal damage. Shiga toxin (Stx), the toxin principle in HUS, is produced locally within the gut following EHEC colonization and is disseminated via the vasculature. Clinical development of HUS currently has no effective treatment and is a leading cause of renal failure in children. Novel post-exposure therapies are currently needed for HUS; therefore, the purpose of this study was to investigate the efficacy of a Stx receptor mimic probiotic in a porcine model of HUS. Edema disease, an infection of swine caused by host adapted Shiga toxin-producing Escherichia coli (STEC) and mediated by Shiga toxin 2e (Stx2e), shares many pathogenic similarities to HUS. In this study, three-week old piglets were inoculated with STEC and 24 hours later treated twice daily with a probiotic expressing an oligosaccharide receptor mimic for Stx2e to determine if the probiotic could reduce intestinal toxin levels.MethodsPiglets were orally inoculated with 1010 CFU of STEC strain S1191 eight days after weaning. Beginning day 1 post-inoculation, piglets were treated orally twice daily with 5 × 1011 CFU of either the receptor mimic probiotic or a sham probiotic for 10 days. Intestinal Stx2e levels were assessed daily via Vero cell assay. The efficacy of the probiotic at reducing intestinal Stx2e, vascular lesions, and clinical disease was evaluated with repeated measures ANOVA and Fisher’s exact test as appropriate.ResultsThe probiotic significantly reduced intestinal Stx2e, as reflected by decreased fecal toxin titers on days 3–8 post-inoculation (p < 0.01). Despite this reduction in intestinal toxin levels, however, the probiotic failed to reduce the incidence of vascular necrosis in target organs and had no effect on clinical disease.ConclusionsThe data suggest that post-exposure treatment with a Stx-binding probiotic is effective in reducing intestinal toxin burden. Future studies could target this approach for possible development of post-exposure interventions.
Highlights
Hemolytic uremic syndrome (HUS) is a systemic and potentially fatal complication of gastroenteritis secondary to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infection characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal damage
A small percentage of patients with diarrhea secondary to EHEC infection develop a systemic and potentially fatal complication known as hemolytic uremic syndrome (HUS), characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal damage
The primary purpose of this study was to assess the ability of this Stx receptor–mimic probiotic to reduce fecal Shiga toxin in a naturally occurring Shiga toxin-producing Escherichia coli (STEC) infection when administered during active infection
Summary
Hemolytic uremic syndrome (HUS) is a systemic and potentially fatal complication of gastroenteritis secondary to Shiga toxin-producing enterohemorrhagic Escherichia coli (EHEC) infection characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal damage. A large outbreak of gastroenteritis and HUS in Germany caused by an atypical enteroaggregative E. coli that produced Shiga toxin (serotype O104:H4), was characterized by a higher prevalence of HUS in adults versus children. In this particular outbreak, 88% of the patients who developed HUS were adults [6,7,8]. HUS treatment involves fluid therapy, dialysis, and management of coagulation disorders; antimicrobial therapy, remains controversial [9,10,11]
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