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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
Statement of
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
Campylobacter jejuni
Neisseria meningitidis
Escherichia coli
Cholera Toxin
Escherichia coli Proteins
Recombinant Proteins
Bacterial Toxins
Description: Copyright © 2005 American Gastroenterological Association Published by Elsevier Inc.
DOI: 10.1053/j.gastro.2005.01.050
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Appears in Collections:Aurora harvest 2
Molecular and Biomedical Science publications

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