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Infect Immun, April 1998, p. 1453-1459, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Pseudomonas aeruginosa Invasion and Cytotoxicity Are Independent Events, Both of Which Involve Protein Tyrosine Kinase Activity

David J. Evans,1 Dara W. Frank,2 Viviane Finck-Barbançon,2 Christine Wu,1 and Suzanne M. J. Fleiszig1,*

School of Optometry, University of California, Berkeley, Berkeley, California 94720,1 and Department of Microbiology, Medical College of Wisconsin, Milwaukee, Wisconsin 532262

Received 5 September 1997/Returned for modification 7 November 1997/Accepted 10 December 1997

Pseudomonas aeruginosa clinical isolates exhibit invasive or cytotoxic phenotypes. Cytotoxic strains acquire some of the characteristics of invasive strains when a regulatory gene, exsA, that controls the expression of several extracellular proteins, is inactivated. exsA mutants are not cytotoxic and can be detected within epithelial cells by gentamicin survival assays. The purpose of this study was to determine whether epithelial cell invasion precedes and/or is essential for cytotoxicity. This was tested by measuring invasion (gentamicin survival) and cytotoxicity (trypan blue staining) of PA103 mutants deficient in specific exsA-regulated proteins and by testing the effect of drugs that inhibit invasion for their effect on cytotoxicity. A transposon mutant in the exsA-regulated extracellular factor exoU was neither cytotoxic nor invasive. Furthermore, several of the drugs that inhibited invasion did not prevent cytotoxicity. These results show that invasion and cytotoxicity are mutually exclusive events, inversely regulated by an exsA-encoded invasion inhibitor(s). Both involve host cell protein tyrosine kinase (PTK) activity, but they differ in that invasion requires Src family tyrosine kinases and calcium-calmodulin activity. PTK inhibitor drugs such as genistein may have therapeutic potential through their ability to block both invasive and cytotoxicity pathways via an action on the host cell.

* Corresponding author. Mailing address: School of Optometry, University of California, Berkeley, CA 94720-2020. Phone: (510) 643-0990. Fax: (510) 643-5109. E-mail: fleiszig{at}socrates.berkeley.edu.




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