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Infection and Immunity, July 1999, p. 3625-3630, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pseudomonas aeruginosa Gene Products PilT and PilU Are Required for Cytotoxicity In Vitro and Virulence in a Mouse Model of Acute Pneumonia

James C. Comolli,1,dagger Alan R. Hauser,1,Dagger Leslie Waite,1,§ Cynthia B. Whitchurch,2 John S. Mattick,2 and Joanne N. Engel1,3,*

Departments of Medicine1 and of Microbiology and Immunology,3 University of California, San Francisco, San Francisco, California 94143, and Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane, Queensland 4072, Australia2

Received 9 February 1999/Returned for modification 23 March 1999/Accepted 9 April 1999

Type IV pili of the opportunistic pathogen Pseudomonas aeruginosa mediate twitching motility and act as receptors for bacteriophage infection. They are also important bacterial adhesins, and nonpiliated mutants of P. aeruginosa have been shown to cause less epithelial cell damage in vitro and have decreased virulence in animal models. This finding raises the question as to whether the reduction in cytotoxicity and virulence of nonpiliated P. aeruginosa mutants are primarily due to defects in cell adhesion or loss of twitching motility, or both. This work describes the role of PilT and PilU, putative nucleotide-binding proteins involved in pili function, in mediating epithelial cell injury in vitro and virulence in vivo. Mutants of pilT and pilU retain surface pili but have lost twitching motility. In three different epithelial cell lines, pilT or pilU mutants of the strain PAK caused less cytotoxicity than the wild-type strain but more than isogenic, nonpiliated pilA or rpoN mutants. The pilT and pilU mutants also showed reduced association with these same epithelial cell lines compared both to the wild type, and surprisingly, to a pilA mutant. In a mouse model of acute pneumonia, the pilT and pilU mutants showed decreased colonization of the liver but not of the lung relative to the parental strain, though they exhibited no change in the ability to cause mortality. These results demonstrate that pilus function mediated by PilT and PilU is required for in vitro adherence and cytotoxicity toward epithelial cells and is important in virulence in vivo.

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

dagger Present address: Department of Bacteriology, University of Wisconsin, Madison, Madison, WI 53706.

Dagger Present address: Department of Microbiology and Immunology, Northwestern University, Chicago, IL 60611.

§ Present address: Department of Obstetrics and Gynecology, University of California, San Francisco, San Francisco, CA 94143.

Infection and Immunity, July 1999, p. 3625-3630, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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