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Pseudomonas aeruginosa cytotoxin as a pathogenicity factor in a systemic infection of leukopenic mice
A L Baltch1, R P Smith, M Franke
1Department of Medicine, Stratton VA Medical Center, NY, USA.
Abstract:
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.
Insights
Pseudomonas aeruginosa cytotoxin significantly increases mortality in leukopenic mice. A specific antibody treatment protected against infection by both high and low cytotoxin-producing strains, demonstrating its protective role.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen.
- Cytotoxins are virulence factors in bacterial infections.
- Leukopenic hosts are susceptible to infections.
Purpose of the Study:
- To investigate the role of Pseudomonas aeruginosa cytotoxin in infection.
- To evaluate the efficacy of a specific antibody in a murine model.
Main Methods:
- Leukopenia was induced in mice using cyclophosphamide.
- Mice were infected with high or low cytotoxin-producing P. aeruginosa strains.
- Mice were pretreated with cytotoxin-specific antibody or control serum.
Main Results:
- The high cytotoxin-producing strain caused significantly higher mortality than the deficient strain.
- Antibody pretreatment reduced mortality in mice infected with both strains.
- Cytotoxin-specific antibody demonstrated a protective effect.
Conclusions:
- P. aeruginosa cytotoxin is a key factor in pathogenicity.
- Cytotoxin-specific antibodies can be protective against P. aeruginosa infection.
- Targeting cytotoxin may be a therapeutic strategy.