Relationship between a low toxicity of the mutant A subunit of enterotoxigenic Escherichia coli enterotoxin and its strong adjuvant action.
In the work described here it was determined if and how unnicking in the A subunit of Escherichia coli enterotoxin at Arg192 or nearby residues affected biological activities of the toxin. The mutant toxin was constructed to lack the nick site in the A subunit by deleting the tripeptide Arg192-Thr193-Ile194, which is essential for toxicity. The mutant toxin did not exhibit agmatine ADP-ribosyltransferase activity in the presence or absence of the ADP-ribosylation factor and had less diarrhoeal activity and lower induction of cyclic AMP than did LT. The mutant toxin exhibited a much stronger adjuvant action on antibody responses to measles virus, keyhole limpt haemocyanin, bovine immunoglobulin and ovalbumin compared with LT. The altered toxicity of the mutant toxin might be closely related to the potent adjuvant action on antibody responses to antigens. The relationship between two activities is discussed.
Tsuji
T
T
Department of Microbiology, Fujita Health University, School of Medicine, Aichi, Japan.
Yokochi
T
T
Kamiya
H
H
Kawamoto
Y
Y
Miyama
A
A
Asano
Y
Y
D036002:ADP Ribose Transferases / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D000242:Cyclic AMP / Q000096:biosynthesis; D003967:Diarrhea / Q000209:etiology; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008459:Measles virus / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D016133:Polymerase Chain Reaction; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D007073:Immunoglobulin E; C027538:heat-labile enterotoxin, E coli; D000242:Cyclic AMP; D036002:ADP Ribose Transferases