Antigenic cross-reactivity and functional inhibition by antibodies to Clostridium difficile toxin A, Streptococcus mutans glucan-binding protein, and a synthetic peptide.
A 10-amino-acid repeating sequence of the hemagglutinating portion of Clostridium difficile toxin A has been synthesized and used to produce antisera in rabbits. Antipeptide antibody inhibited toxin A-mediated hemagglutination and neutralized cytotoxic activity. Immunoblot analysis with the antipeptide antibody revealed cross-reactivity with native toxin, a recombinant protein containing the toxin A repeats, and a glucan-binding protein from Streptococcus mutans whose primary structure has repeating amino acid motifs similar to those of the synthetic peptide. A polyclonal antibody against the glucan-binding protein, which cross-reacted with purified toxin A, also inhibited toxin A-mediated hemagglutination and neutralized cytotoxic activity. We recently identified toxin A and the glucan-binding protein as members of a novel family of clostridial and streptococcal binding proteins based on conserved repeating amino acid motifs at the C-terminal region of the molecules. This study provides immunological and functional evidence of the predicted relationship between toxin A and the glucan-binding protein and further implicates the repeating subunits as ligand-binding domains in this family of proteins.
Wren
B W
BW
Department of Medical Microbiology, St. Bartholomew's Hospital Medical College, West Smithfield, London, United Kingdom.
Russell
R R
RR
Tabaqchali
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D016360:Clostridioides difficile / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005936:Glucans / Q000276:immunology*; D006384:Hemagglutination / Q000276:immunology; D015151:Immunoblotting; D037102:Lectins; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D013295:Streptococcus mutans / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D002352:Carrier Proteins; D004768:Enterotoxins; D000939:Epitopes; D005936:Glucans; D037102:Lectins; D009842:Oligopeptides; D011994:Recombinant Proteins; C037937:glucan-binding proteins; C041348:tcdA protein, Clostridium difficile