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Infection and Immunity, April 2002, p. 2198-2205, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2198-2205.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Pseudomonas aeruginosa ExoT Acts In Vivo as a GTPase-Activating Protein for RhoA, Rac1, and Cdc42

B. I. Kazmierczak1,{dagger} and J. N. Engel1,2,3*

Departments of Medicine,1 Microbiology and Immunology,2 Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 941433

Received 24 July 2001/ Returned for modification 25 September 2001/ Accepted 9 January 2002

The Pseudomonas aeruginosa protein ExoT is a bacterial GTPase-activating protein (GAP) that has in vitro activity toward Rho, Rac, and Cdc42 GTPases. Expression of ExoT both inhibits the internalization of strain PA103 by macrophages and epithelial cells and is associated with morphological changes (cell rounding and detachment) of infected cells. We find that expression of ExoT leads to the loss of GTP-bound RhoA, Rac1, and Cdc42 in transfected HeLa cells, demonstrating that ExoT has GAP activity in vivo toward all three GTPases. GAP activity is absolutely dependent on the presence of arginine at position 149 but is not affected by whether ExoT is expressed in the absence or presence of other P. aeruginosa type III secreted proteins. We also demonstrate that expression of ExoT in epithelial cells is sufficient to cause stress fiber disassembly by means of ExoT's GAP activity toward RhoA.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Disease, University of California, San Francisco, 521 Parnassus Ave., Box 0654, Room C44, San Francisco, CA 94143-0654. Phone: (415) 476-7355. Fax: (415) 476-9364. E-mail: Jengel{at}medicine.ucsf.edu.

Editor: D. L. Burns

{dagger} Present address: Department of Internal Medicine, Yale University, New Haven, CT 06520-8022.

Infection and Immunity, April 2002, p. 2198-2205, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2198-2205.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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