The carboxyl terminal amino acid residues of Pseudomonas aeruginosa exotoxin A involved in cell toxicity and pathogenesis, characterized by a neutralizing human monoclonal antibody

• Published in: Biochemical and biophysical research communications Vol. 180; no. 3; p. 1498
• Main Authors: Ohtsuka, H, Higuchi, A, Nomura, N, Horigome, K, Kohzuki, T, Nakamori, Y, Noguchi, H
• Format: Journal Article
• Language: English
• Published: United States 14-11-1991
• Subjects: 3T3 Cells; ADP Ribose Transferases; Animals; Antibodies, Monoclonal - therapeutic use; Bacterial Toxins; Carrier Proteins; Cell Survival - drug effects; Chromosome Deletion; Enzyme-Linked Immunosorbent Assay; Epitopes - analysis; Exotoxins - genetics; Exotoxins - immunology; Exotoxins - toxicity; Genes, Bacterial; Humans; Immunotherapy; Male; Mice; Mice, Inbred ICR; Neutralization Tests; Peptide Fragments - isolation & purification; Peptide Fragments - metabolism; Poly(ADP-ribose) Polymerase Inhibitors; Pseudomonas aeruginosa - pathogenicity; Pseudomonas aeruginosa Exotoxin A; Pseudomonas Infections - immunology; Receptors, Cell Surface; Receptors, Cholinergic - metabolism; Recombinant Proteins - immunology; Recombinant Proteins - toxicity; Virulence Factors
• ISSN: 0006-291X
• DOI: 10.1016/S0006-291X(05)81365-8

Human monoclonal antibody HI-1A4 (IgG3, lambda) neutralized a toxicity caused by pseudomonal exotoxin A (Ex-A) in cell culture and in vivo, and was effective in experimental Pseudomonas aeruginosa infections in mice. HI-1A4 inhibited an Ex-A catalyzed ADP-ribosylation of elongation factor 2 but did not inhibit an incorporation of toxin into a target cell at all. One molecule of HI-1A4 neutralized at least 2 molecules of Ex-A. HI-1A4 retained its binding activity at pH 4.0. The epitope region for HI-1A4 was demonstrated to be a carboxyl terminal end of amino acid residues 591-613 of Ex-A. HI-1A4 might bind to Ex-A carboxyl terminal region outside a target cell, be incorporated into cells as a complex with Ex-A, and inhibit the intracellular function in which the carboxyl terminal part of Ex-A was involved, resulting in the interruption of intoxication of Ex-A.