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Infect Immun, July 1998, p. 3242-3249, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro Cellular Toxicity Predicts Pseudomonas aeruginosa Virulence in Lung Infections

Teiji Sawa,1 Maria Ohara,1 Kiyoyasu Kurahashi,1 Sally S. Twining,2 Dara W. Frank,3 David B. Doroques,1 Taicy Long,1 Michael A. Gropper,1 and Jeanine P. Wiener-Kronish1,*

Departments of Anesthesia and Medicine, Cardiovascular Research Institute, The University of California, San Francisco, California 94143,1 and Department of Biochemistry2 and Department of Microbiology,3 Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Received 21 January 1998/Returned for modification 30 March 1998/Accepted 29 April 1998

The role of quorum sensing by Pseudomonas aeruginosa in producing cytotoxicity has not been fully investigated. Strains of P. aeruginosa have been characterized as having an invasive or a cytotoxic phenotype (S. M. J. Fleiszig et al., Infect. Immun. 65:579-586, 1997). We noted that the application of a large inoculum of the invasive strain 6294 caused cytotoxicity of cultured epithelial cells. To investigate this dose-related cytotoxicity, we compared the behavior of 6294 to that of another invasive strain, PAO1, and determined whether the cytotoxicity could be related to quorum sensing. Both invasive strains, 6294 and PAO1, appear to have quorum-sensing systems that were operative when large doses of bacteria were applied to cultured lung epithelial cells or instilled into the lungs of animals. Nonetheless, only 6294 was cytotoxic. Cytotoxicity induced by 6294 correlated with increased elastase production. These experiments suggest that there are multiple mechanisms 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 utilizing a range of bacteria-to-cell ratios. It appears that quorum sensing may inversely correlate with virulence in that strains that produced PAI [N-(3-oxododecanoyl) homoserine lactone] also appeared to attract more polymorphonuclear leukocytes in vivo and were possibly eliminated more quickly. In addition, exoproduct production in bacteriological medium in vitro may differ significantly from exoproduct expression from infections in vivo or during cocultivation of bacteria with tissue culture cells.

* Corresponding author. Mailing address: Department of Anesthesia and Critical Care Medicine, The University of California, San Francisco, CA 94143. Phone: (415) 476-8968. Fax: (415) 476-5434. E-mail: jwk{at}jemo.ucsf.edu.

Infect Immun, July 1998, p. 3242-3249, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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