IN-VITRO CELLULAR TOXICITY PREDICTS PSEUDOMONAS-AERUGINOSA VIRULENCE IN LUNG INFECTIONS

The role of quorum sensing by Pseudomonas aeruginosa in producing cyto toxicity has not been fully investigated. Strains of P. aeruginosa hav e been characterized as having an invasive or a cytotoxic phenotype (S . M. J. Fleiszig et al., Infect. Immun. 65:579-586, 1997). We noted th at the application of a large inoculum of the invasive strain 6291 cau sed cytotoxicity of cultured epithelial cells. To investigate this dos e-related cytotoxicity, we compared the behavior of 6294 to that of an other invasive strain, PAO1, and determined whether the cytotoxicity c ould be related to quorum sensing. Both invasive strains, 6291 and PAO 1, appear to have quorum-sensing systems that were operative when larg e doses of bacteria were applied to cultured lung epithelial cells or instilled into the lungs of animals. Nonetheless, only 6294 was cytoto xic. Cytotoxicity induced by 6294 correlated with increased elastase p roduction. These experiments suggest that there are multiple mechanism s for the induction of cytotoxicity, pathology, and mortality in vivo. However, in vivo cytotoxicity and mortality, but not pathology, could be predicted by quantitative in vitro cellular damage experiments uti lizing a range of bacteria-to-cell ratios. It appears that quorum sens ing may inversely correlate with virulence in that strains that produc ed PAI [N-(3-oxododecanoyl) homoserine lactone] also appeared to attra ct more polymorphonuclear leukocytes in vivo and were possibly elimina ted more quickly. In addition, exoproduct production in bacteriologica l medium in vitro may differ significantly from exoproduct expression from infections in vivo or during cocultivation of bacteria with tissu e culture cells.