Experimental infections with protease-deficient mutants of Pseudomonas aeruginosa in mice.

The virulence of a protease-producing strain of Psuedomonas aeruginosa was compared with that of mutants that had lost the ability to produce proteases and other extracellular enzymes. Lethal infections were produced by inoculating mice intraperitoneally with bacteria in mucin, or by inoculating mice intraperitoneally or intravenously with bacteria 4 days after treatment with cyclophosphamide, 200 mg per kg body weight. No significant difference in virulence between the wild-type parent strain and some of its protease-deficient mutants was found. Histopatholoical examination of different organs in the cyclophosphamide-treated and infected mice showed striking fatty infiltration and focal necrosis of liver, multiple necrotic foci in the spleen and haemorrhagic cystitis with necorsis. The cystitis was produced by cyclophosphamide alone but was aggravated by the infection. In conclusion, no correlation between the production of protease in broth culture and the ability to produce lethal septicaemia in mice was found, and extracellular proteases probably didnot contribute to the virulence of P. aeruginosa. However, the histopathological changes in the liver suggested a role for exotoxin A insystemic infections.