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-infected mice with the protease inhibitor alpha 2-macroglobulin but not treatment with phosphoramidon enhanced survival. Treatment with alpha 2-macroglobulin caused reductions in bacterial counts in the skin and livers of infected mice and also protected liver elongation 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 opsonizing antibodies in the preparation. The protective capacity of the IgG could be removed by its adsorption with heat-killed cells of the strain used for infecting the mice. The protection afforded by alpha 2-macroglobulin was not due to the presence of opsonizing antibodies 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 organisms 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 pseudomonas infections of burn wounds with protease inhibitors may serve as an alternative to antibiotic treatment and/or immunotherapy.