CORRELATION OF PSEUDOMONAS-AERUGINOSA VIRULENCE FACTORS FROM CLINICALAND ENVIRONMENTAL ISOLATES WITH PATHOGENICITY IN THE NEUTROPENIC MOUSE

The potential pathogenicity of a microorganism is a major concern for Health Canada evaluators, who will be processing new biotechnology pro ducts under the Canadian Environmental Protection Act. Potential patho genicity is generally predicted by the results of animal pathogenicity studies. In an attempt to define surrogate data for an animal model, this study was initiated. Pseudomonas aeruginosa isolates from clinica l and environmental sources were screened for their pilus type, seroty pe, lipopolysaccharide type, ability to evade host responses, and prod uction of toxin A, exoenzyme S, elastase, phospholipase C, and total p rotease. The 50% lethal dose (LD50) of the same isolates was determine d in the neutropenic mouse model of infection. An attempted correlatio n was drawn between each (or combinations) of the virulence determinan ts and the LD50. Stepwise linear regression showed that the presence o f high levels of exoenzyme S in association with elastase or phospholi pase C, or to a minor extent toxin A, was correlated with low numbers of bacteria required to elicit an LD50. No correlation between any of the other factors examined and virulence was detected. The data sugges t that an in vitro high level of exoenzyme S production could be used as surrogate information for neutropenic mouse modelling; however, the levels of all of the extracellular enzymes should be considered when making such an assessment.