Article

Recombinant probiotics for treatment and prevention of enterotoxigenic Escherichia coli diarrhea.

School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia.
Gastroenterology (impact factor: 11.68). 06/2005; 128(5):1219-28. DOI:S0016508505001629 [pii] pp.1219-28
Source: PubMed

ABSTRACT 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.
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.
The strongest heat-labile enterotoxin binding was achieved with a construct (CWG308:pLNT) that expresses a mimic of lacto-N-neotetraose, which neutralized > or = 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.
Toxin-binding probiotics such as those described here have considerable potential for prophylaxis and treatment of enterotoxigenic Escherichia coli-induced travelers' diarrhea.

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Keywords

bacterial toxins
 
binding heat-labile enterotoxin
 
diverse enterotoxigenic Escherichia coli strains
 
enterotoxigenic Escherichia coli strains
 
enterotoxigenic Escherichia coli-induced travelers' diarrhea
 
ganglioside GM2
 
harmless Escherichia coli strain
 
harmless gut bacteria
 
heat-labile enterotoxin activity
 
heat-labile enterotoxin-induced fluid secretion
 
molecular mimicry
 
own weight
 
produce heat-labile enterotoxin
 
purified heat-labile enterotoxin
 
rabbit ligated ileal loops
 
recombinant probiotic
 
strongest heat-labile enterotoxin binding
 
therapeutic strategy
 
Toxin-binding probiotics
 
Weaker toxin neutralization