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Experimental infections with protease-deficient mutants of Pseudomonas aeruginosa in mice (Plate VIII)

Department of Clinical Microbiology, Karolinska Hospital, S-10401 Stockholm, Department of Bacteriology, National Bacteriological Laboratory, S-10521 Stockholm

^*National Veterinary Institute, S-10405 Stockholm

^*National Board of Occupational Safety and Health, S-10026 Stockholm, Sweden

Received July 11, 1977
Accepted October 1, 1977

The virulence of a protease-producing strain of Pseudomonas 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. Histopathological 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 necrosis. 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 did not contribute to the virulence of P. aeruginosa. However, the histopathological changes in the liver suggested a role for exotoxin A in systemic infections.