The role of exotoxin A in pseudomonas disease and immunity

Exotoxin A is an extracellular enzyme that is produced by most clinical strains of Pseudomonas aeruginosa. It is a single-chain polypeptide (molecular weight, 71,000) with A and B fragments that mediate enzymatic and cell-binding functions, respectively. Exotoxin A catalyzes the transfer of the adenosine diphosphate-ribosyl moiety from nicotinamide-adenine dinucleotide to elongation factor 2, which results in the inactivation of the latter and the inhibition of protein biosynthesis. Exotoxin A is a potent cytotoxin and is lethal for a variety of animals, including subhuman primates. Produced in vivo during P. aeruginosa infections, exotoxin A apparently causes disease by inhibition of protein synthesis, direct cytopathic effects, and interference with cellular immune functions of the host. Antibodies to exotoxin A provide protection from some of the biochemical, pathologic, and lethal consequences of both experimental and clinical pseudomonas infections. Toxoid produced from exotoxin A is currently undergoing evaluation as a vaccine for possible use in the immunoprophylaxis against pseudomonas disease in humans.