Tissue binding properties of the cholera toxin

The control of Pseudomonas aeruginosa infection continues to pose a serious problem in many clinical conditions. Despite intense efforts, the exact mechanism of pathogenicity remains unknown. Lethality in experimental infection was found due to the in vivo elaboration of a lethal factor(s) produced early in the infectious process, preceding increases in the microbial population which appeared to occur as a terminal event. The extracellular slime of P. aeruginosa has received serious attention and possesses the characteristics of a virulence factor and acts as a protective antigen. More recently, highly purified preparations of slime have been shown to produce toxic manifestations, leucopenia, and death of mice. These events were found to be indistinguishable from those observed during lethal infection produced with viable bacilli. Furthermore, purified slime was also shown to markedly inhibit phagocytosis. The production of extracellular slime is considered to be a species characteristic of P. aeruginosa, and in vitro production has been reported under various cultural conditions. However, the in vivo production of extracellular slime has not been reported. The purpose of this study was to demonstrate the in vivo production of slime and its appearance in the peripheral circulation of mice infected with P. aeruginosa as further support for the possible role of slime in experimental infection. Although its use is well established in the Pseudomonas literature, in this paper the term 'slime' specifically refers to the refined polysaccharide containing component isolated from the extracellular slime layer. Indirect hemagglutination inhibition tests were employed to detect slime in concentrations as low as 1 μg/ml. Increasing concentrations of slime resulted in proportionately greater inhibition of hemagglutination. Peritoneal aspirates and plasma of mice injected with slime were shown to exhibit the inhibitory activity of slime. The rapid dissemination of slime into the peripheral circulation was also indicated by the hemagglutination of mouse erythrocytes by specific anti slime serum. By similar methods, the inhibitory activity of slime was also detected in peritoneal aspirates and plasma of mice infected with lethal doses of viable P. aeruginosa. Furthermore, the inhibitory activity was found to increase with time after viable cell infection, whereas such increases were not detected after the injection of heat killed organisms. Ferritin labeled slime antibodies were found to completely surround cells of P. aeruginosa obtained from the peritoneal cavity of mice 5 h postinfection.