Experimental Studies of the Pathogenesis of Infections Due to Pseudomonas aeruginosa: Effect of Treatment with Protease Inhibitors

Data are presented showing that treatment of burned, Pseudomonas aeruginosa-in-fected mice with the protease inhibitor a2-macroglobulin but not treatment with phos-phoramidon enhanced survival. Treatment with a2-macroglobulin caused reductions in bacterial counts in the skin and livers of infected mice and also protected liver elonga-tion factor 2. Similar results were observed when human IgG was used for treatment. The protective effect of the IgG treatment was probably due to the presence of opsoniz-ing antibodies in the preparation. The protective capacity of the IgG could be removed by its adsorption with heat-killed cellsof the strain used for infecting the mice. The pro-tection afforded by a2-macroglobulin was not due to the presence of opsonizing anti-bodies in the preparation used. It appeared to be due to inhibition of the proteolytic, not the elastolytic, activities of alkaline protease and elastase elaborated by the organ-isms growing in the burned skin tissue. Proteolytic activities of these enzymes appeared to serve as virulence factors in P. aeruginosa by decreasing the generation time in vivo of the microorganisms growing in the burned skin tissue and by allowing the organisms to spread from this local site into the systemic circulation. Treatment of pseudomona