Abstract
The incidence of production and biological activity of various extracellular factors of Pseudomonas aeruginosa from leukaemic and non-leukaemic patients were investigated. A panel of 157 isolates was constructed from blood of leukaemic (Group I), and other body sites of the same patients (Group II), and from various specimens of non-leukaemic patients (Group III). Most strains produced pyocyanin. Cross infection between patients was not a significant problem. The incidence of protease production was high (94%) and there was no significant quantitative difference between strains. Protease production was inhibited by plasma a2 macroglobulin but urine was not inhibitory for the enzyme. Protease activity was demonstrated with fibronectin by a specific ELISA. Complement degradation, particularly C3, was also demonstrated by gel electrophoresis and immunoglobulins IgG, M and A were destroyed by HPLC purified alkaline protease. The molecular weight of alkaline protease was found to be 36 kd and that of elastase to be 22 kd. All isolates produced a cytotoxin in plasma active on polymorphonuclear (PMN) leucocytes. Cytotoxic proteins purified by FPLC exhibited a wide range of molecular weights. Various ELISA assays were developed for the detection of exotoxin A production. The incidence of toxin was similar in each group. Exotoxin A was rare in urines from infected patients, but was frequent in serum especially from chronic infections. Exotoxin A levels in sera of leukaemic patients was low. Antibody to exotoxin A was also low and anomalous results were obtained. Haemolytic activity was universal for all isolates and much of this was due to heat-stable glycolipid. A hypothetical model of interaction between exotoxin A production and cytotoxin is proposed in which the cytotoxin of P. aeruginosa cause lysis of leucocytes with the resultant release of leucocyte elastase enzyme which is highly active on exotoxin A. Neutropenic patients lack target cells for cytotoxin and thus exotoxin A activity is unchecked.