Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/27612
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Type: Journal article
Title: Recombinant probiotics for treatment and prevention of enterotoxigenic escherichia coli diarrhea
Author: Paton, A.
Jennings, M.
Morona, R.
Wang, H.
Focareta, A.
Roddam, L.
Paton, J.
Citation: Gastroenterology, 2005; 128(5):1219-1228
Publisher: W B Saunders Co
Issue Date: 2005
ISSN: 0016-5085
1528-0012
Statement of
Responsibility: 
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.
RMID: 0020052737
DOI: 10.1053/j.gastro.2005.01.050
Published version: http://www.gastrojournal.org/home
Appears in Collections:Molecular and Biomedical Science publications

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