Role of exotoxin A and proteases of Pseudomonas aeruginosa in respiratory tract infections.

Hamster tracheal organ culture has been used to study the role of exotoxin A and proteases of Pseudomonas aeruginosa in infections of the respiratory tract. Tracheal explants infected with a toxin producing, protease producing strain or a toxin deficient, protease producing strain displayed evidence of exfoliation and disorganization of the tracheal of the tracheal epithelium 12 h after initiation of infection. A toxin producing protease deficient strain caused some desquamation of cells and cellular swelling, but exfoliation was not evident. Each of the toxin producing and (or) protease producing strains inhibited protein synthesis of the explants. Purified exotoxin inhibited protein synthesis and caused some pathological changes similar to those observed with the toxin producing strain. Purified elastase from P. aeruginosa only inhibited protein synthesis at 10 microgram/mL but caused exfoliation at 0.01 microgram/mL. Alkaline protease had no detectable effect on the explants. The effects of active infection could be prevented by treatment with gentamycin. All the strains tested caused an inhibition of ciliary activity, but no correlation could be made with any of the extracellular products. Exotoxin A and elastase may be responsible for much of the destruction of respiratory tract tissue in Pseudomonas infections although other bacterial factors and host factors are of importance.