Gangliosides bacterial binding

Fig. 8.7 CTB-GM1-ganglioside binding ELISA assay. Plates, coated first with GMrganglioside and bovine serum albumin (BSA), respectively, were irrigated with total soluble plant protein from chloroplast transgenic lines (3 and 7) and 300 ng of purified bacterial CTB. The absorbance of the GM1-ganglioside-CTB-antibody complex in each case was measured at 405 nm. Total soluble protein from untransformed plants was used as the negative control.

Two of the most widely spread and well-studied enterotoxigenic forms of bacterial diarrhea are ETEC and Vibrio cholerae. The toxins they produce, labile toxin (LT) and cholera toxin (CT) respectively, are very similar in primary sequence, structure, and mechanism of action [72]. They are homologous multi-subunit proteins in which the non-toxic B subunit mediates GMj ganglioside binding, and thus are candidates for vaccines that can neutralize toxin activity. 

Cholera toxin consists of one 240-residue A subunit and a ring of five 103-residue B subunits.c e The latter is a "targeting complex," a bacterial lectin each subunit of which binds to the galactose and sialic acid termini of a single molecule of ganglioside Gm1. 

Niemann H (1991) Molecular biology of clostridial neurotoxins. In Alouf J, Freer J (eds) A source-book of bacterial protein toxins. Academic Press, London, pp 303 18 Nishiki T, Tokuyama Y, Kamata Y, Nemoto Y, Yoshida A et al. (1996) The high-affinity binding of Clostridium botulinum type b neurotoxin to synaptotagmin ii associated with gangliosides gtlb/gdla. FEBS Lett 378 253-7... 

Fishman PH (1982) Role of membrane gangliosides in the binding and action of bacterial toxins. In J. Membr. Biol. 69 85-97. 

It should also be mentioned that several bacterial toxins are known which bind to gangliosides in a sialic-acid-dependent manner, e.g. cholera, pertussis and tetanus toxins... 

A bacterial enterotoxin related to cholera toxin is also a target for a multivalent inhibitor. When ingested, the enterotoxin s five identical binding sites recognize and bind to ganglioside carbohydrate groups in the gut lining (163). 

With all these more or less specific interactions shown by gangliosides, the question may be raised as to the involvement and the role played in those events by the two heterophilic molecular moieties of the glycolipid. VJe therefore chose two bacterial toxins, tetanus toxin and cholera toxin, to perform binding studies which were aimed at a further identification of the nature of the protein fixation by the sialo-glycolipid. 

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