title: Sialyloligosaccharides inhibit cholera toxin binding to the GM1 receptor.
abstract: It is recognised that cholera toxin (Ctx) is a significant cause of gastrointestinal disease globally, particularly in developing countries where access to uncontaminated drinking water is at a premium. Ctx vaccines are prohibitively expensive and only give short-term protection. Consequently, there is scope for the development of alternative control strategies or prophylactics. This may include the use of oligosaccharides as functional mimics for the cell-surface toxin receptor (GM1). Furthermore, the sialic acid component of epithelial receptors has already been shown to contribute significantly to the adhesion and pathogenesis of Ctx. Here, we demonstrate the total inhibition of Ctx using GM1-competitive ELISA with 25mgmL(-1) of a commercial preparation of sialyloligosaccharides (SOS). The IC(50) value was calculated as 5.21mgmL(-1). One-hundred percent inhibition was also observed at all concentrations of Ctx-HRP tested with 500ngmL(-1) GM1-OS. Whilst SOS has much lower affinity for Ctx than GM1-OS, the commercial preparation is impure containing only 33.6% carbohydrate; however, the biantennary nature of SOS appears to give a significant increase in potency over constituent monosaccahride residues. It is proposed that SOS could be used as a conventional food additive, such as in emulsifiers, stabilisers or sweeteners, and are classified as nondigestible oligosaccharides that pass into the small intestine, which is the site of Ctx pathogenesis.
authors.affiliation: Department of Food Biosciences, University of Reading, Whiteknights, Reading RG6 6AP, UK.
authors.forename: Haydn R
authors.initials: HR
authors.lastname: Sinclair
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Smejkal
authors.forename: Claire
authors.initials: C
authors.lastname: Glister
authors.forename: Fred
authors.initials: F
authors.lastname: Kemp
authors.forename: Ellen
authors.initials: E
authors.lastname: van den Heuvel
authors.forename: Jaap
authors.initials: J
authors.lastname: de Slegte
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gibson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rastall
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002772:Cholera Toxin / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000378:metabolism*; D005690:Galactose / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007421:Intestine, Small / Q000378:metabolism; D007785:Lactose / Q000737:chemistry; D009005:Monosaccharides / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D009005:Monosaccharides; D009844:Oligosaccharides; C016735:sialooligosaccharides; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D007785:Lactose; D005690:Galactose