Inhibition of cholera toxin binding to membrane receptors by pig gastric mucin-derived glycopeptides: differential effect depending on the ABO blood group antigenic determinants

Abstract

The capacity of pig gastric mucin-derived glycopeptides to interfere with the binding of cholera toxin (CT) to membrane receptors was studied. Two types of glycopeptide preparations with or without human blood group A antigenic activity were assayed for comparison in a system in which the target for the toxin was rat erythrocyte ghosts. Blood group A-active glycopeptides (A+ glycopeptides) were more potent inhibitors for the toxin binding than those lacking group A activity (A- glycopeptides). The mean values of the 50% inhibitory dose revealed that the A+ glycopeptide preparations were 6.6-fold-more potent inhibitors than the A- ones (P less than 0.001). The inhibitory capacity of the different A+ glycopeptide preparations was not directly proportional to the group A antigenic titer. The A+ glycopeptides showed a higher capacity than the A- glycopeptides to interact with the toxin as revealed by CT-glycopeptide complex formation, which could be detected by Sephacryl S-400 chromatography. This result suggests that glycopeptide inhibition of CT binding to the erythrocyte ghosts is mediated by a competition between the GM1 receptors and the glycopeptides for the toxin. The differential effect between both types of glycoconjugates was independent of the way of measuring the amount of glycopeptides used (dry weight, carbohydrate or protein content). The existence in the gastrointestinal tract of mucins not carrying or carrying different ABO blood group determinants, which could behave as more or less potent inhibitors of CT binding to membrane receptors, may help to explain the relationship between ABO blood groups and severity of cholera.

A monoclonal antibody, PGM34, against 6‐sulfated blood‐group H type 2 antigen, on the carbohydrate moiety of mucin

“…For instance, A1-6 may contain the 6-sulfated blood group A sequence. This is possible because oligosaccharides with the blood group A sequence are present in pig gastric mucin [18], although they do not have the sulfate residue. If this is the case, the addition of GalNAc to Gal may cause loss of reactivity with PGM34.…”

Mucins as multifunctional building blocks of biomaterials

“…However, mucins are the closest to their original conformation when presented in solutions or gels. Mucin gels and solutions have been used to investigate mucins' protective role against microbes, 58-61 viruses 62,63 and toxins 64,65 (Fig. 3A).…”

Fucosylation and protein glycosylation create functional receptors for cholera toxin

“…While LTB is known to bind both GM1 and glycoprotein receptors, GM1 is commonly described to be the sole host cell receptor recognized by CTB ( Foster and Baron, 1996 ). However, a variety of experimental approaches have pointed to the possibility that CTB may also recognize glycoproteins present on mammalian cells ( Morita et al, 1980 ; Monferran et al, 1990 ; Balanzino et al, 1994 ; Platt et al, 1997 ; Hansen et al, 2005 ; Blank et al, 2007 ; Day et al, 2012 ). Indeed, CTB binding to cells does not uniformly parallel GM1 levels, implying the existence of additional CTB-binding molecules ( Platt et al, 1997 ; Yanagisawa, 2006 ).…”