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|Title:||Recombinant probiotics for treatment and prevention of enterotoxigenic escherichia coli diarrhea|
|Citation:||Gastroenterology, 2005; 128(5):1219-1228|
|Publisher:||W B Saunders Co|
|Adrienne W. Paton, Michael P. Jennings, Renato Morona, Hui Wang, Antonio Focareta, Louise F. Roddam and James C. Paton|
|Abstract:||Background & Aims: We have developed a therapeutic strategy for gastrointestinal infections that is based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. The aim of this study was to apply this to the development of a recombinant probiotic for treatment and prevention of diarrheal disease caused by enterotoxigenic Escherichia coli strains that produce heat-labile enterotoxin. Methods: This was achieved by expressing glycosyltransferase genes from Neisseria meningitidis or Campylobacter jejuni in a harmless Escherichia coli strain (CWG308), resulting in the production of a chimeric lipopolysaccharide capable of binding heat-labile enterotoxin with high avidity. Results: The strongest heat-labile enterotoxin binding was achieved with a construct (CWG308:pLNT) that expresses a mimic of lacto-N-neotetraose, which neutralized ≥93.8% of the heat-labile enterotoxin activity in culture lysates of diverse enterotoxigenic Escherichia coli strains of both human and porcine origin. When tested with purified heat-labile enterotoxin, it was capable of adsorbing approximately 5% of its own weight of toxin. Weaker toxin neutralization was achieved with a construct that mimicked the ganglioside GM2. Preabsorption with, or coadministration of, CWG308:pLNT also resulted in significant in vivo protection from heat-labile enterotoxin-induced fluid secretion in rabbit ligated ileal loops. Conclusions: Toxin-binding probiotics such as those described here have considerable potential for prophylaxis and treatment of enterotoxigenic Escherichia coli–induced travelers’ diarrhea.|
|Keywords:||Ileum; Adrenal Glands; Cells, Cultured; Animals; Rabbits; Campylobacter jejuni; Neisseria meningitidis; Escherichia coli; Diarrhea; Glycosyltransferases; Cholera Toxin; Lipopolysaccharides; Escherichia coli Proteins; Recombinant Proteins; Bacterial Toxins; Enterotoxins; Probiotics|
|Description:||Copyright © 2005 American Gastroenterological Association Published by Elsevier Inc.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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