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Infection and Immunity, October 1999, p. 5530-5537, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pseudomonas aeruginosa Induces Type-III-Secretion-Mediated Apoptosis of Macrophages and Epithelial Cells

Alan R. Hauser1,dagger and Joanne N. Engel1,2,*

Departments of Medicine1 and Microbiology and Immunology,2 University of California, San Francisco, San Francisco, California 94143

Received 22 April 1999/Returned for modification 14 June 1999/Accepted 16 July 1999

Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that is cytotoxic towards a variety of eukaryotic cells. To investigate the effect of this bacterium on macrophages, we infected J774A.1 cells and primary bone-marrow-derived murine macrophages with the P. aeruginosa strain PA103 in vitro. PA103 caused type-III-secretion-dependent killing of macrophages within 2 h of infection. Only a portion of the killing required the putative cytotoxin ExoU. By three criteria, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assays, cytoplasmic nucleosome assays, and Hoechst staining, the ExoU-independent but type-III-secretion-dependent killing exhibited features of apoptosis. Extracellular bacteria were capable of inducing apoptosis, and some laboratory and clinical isolates of P. aeruginosa induced significantly higher levels of this form of cell death than others. Interestingly, HeLa cells but not Madin-Darby canine kidney cells were susceptible to type-III-secretion-mediated apoptosis under the conditions of these assays. These findings are consistent with a model in which the P. aeruginosa type III secretion system transports at least two factors that kill macrophages: ExoU, which causes necrosis, and a second, as yet unidentified, effector protein, which induces apoptosis. Such killing may contribute to the ability of this organism to persist and disseminate within infected patients.

* 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 Microbiology and Immunology, Northwestern University, Chicago, IL 60611.

Infection and Immunity, October 1999, p. 5530-5537, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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