Pseudomonas aeruginosa cytotoxin as a pathogenicity factor in a systemic infection of leukopenic mice.
The effect of Pseudomonas aeruginosa cytotoxin was assessed in leukopenic outbred Swiss male mice (20 g) using a high cytotoxin-producing strain (PA158) and its cytotoxin-deficient isogenic mutant (PA114F5) generated by Tn7::Tn5 transposon mutagenesis of PA158. Leukopenia was induced by intraperitoneal (i.p.) administration of cyclophosphamide (150 micrograms/g). Anesthetized mice were infected via a 4 mm incision on the shaved back with 300 CFU/mouse (9 LD50; expected death rate 85%). Precleared mouse cytotoxin-specific heat inactivated rabbit polyclonal antibody (RPA) was administered i.p. (0.2 ml) 24 hr before challenge. Controls received i.p. normal rabbit serum, RPA, cyclophosphamide alone, or a sham procedure. Challenge with the high cytotoxin-producing strain PA158 caused earlier and a significantly greater mortality than that observed with a cytotoxin-deficient strain PA114F5 (P < 0.01). Cytotoxin-specific polyclonal antibody was protective. Pretreatment with antibody decreased the mortality rate following challenge with PA158 from 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 contributes to the pathogenicity of the organism and that cytotoxin antibody is protective in a systemic P. aeruginosa infection in leukopenic mice.
Baltch
A L
AL
Department of Medicine, Stratton VA Medical Center, NY, USA.
Smith
R P
RP
Franke
M
M
Ritz
W
W
Michelsen
P
P
Bopp
L
L
Lutz
F
F
D000704:Analysis of Variance; D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use; D007956:Leukocidins / Q000502:physiology / Q000633:toxicity*; D007970:Leukopenia / Q000150:complications*; D008297:Male; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D013045:Species Specificity
D000907:Antibodies, Bacterial; D007956:Leukocidins