PSEUDOMONAS-AERUGINOSA CYTOTOXIN AS A PATHOGENICITY FACTOR IN A SYSTEMIC INFECTION OF LEUKOPENIC MICE

The effect of Pseudomonas aeruginosa cytotoxin was assessed in leukope nic outbred Swiss male mice (20 g) using a high cytotoxin-producing st rain (PA158) and its cytotoxin-deficient isogenic mutant (PA114F5) gen erated by Tn7::Tn5 transposon mutagenesis of PA 158. Leukopenia was in duced by intraperitoneal (i.p.) administration of cyclophosphamide (15 0 mu g/g). Anesthetized mice were infected via a 4 mm incision on the shaved back with 300 CFU/mouse (9 LD(50); expected death rate 85%). Pr ecleared mouse cytotoxin-specific heat inactivated rabbit polyclonal a ntibody (RPA) was administered i.p. (0.2 ml) 24 hr before challenge. C ontrols received i.p. normal rabbit serum, RPA, cyclophosphamide alone , or a sham procedure. Challenge with the high cytotoxin-producing str ain PA158 caused earlier and a significantly greater mortality than th at observed with a cytotoxin-deficient strain PA114F5 (P < 0.01). Cyto toxin-specific polyclonal antibody was protective. Pretreatment with a ntibody decreased the mortality rate following challenge with PA158 fr om 88.9% to 27.8% (P < 0.01). Pretreatment with antibody decreased the mortality rate following challenge with PA114F5 from 27.8% to 5.6% (P < 0.05). These results demonstrate that P. aeruginosa cytotoxin contr ibutes to the pathogenicity of the organism and that cytotoxin antibod y is protective in a systemic P. aeruginosa infection in leukopenic mi ce.