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Infection and Immunity, April 2001, p. 2675-2683, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2675-2683.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pseudomonas aeruginosa-Induced Apoptosis Involves Mitochondria and Stress-Activated Protein Kinases

Verena Jendrossek,1 Heike Grassmé,2 Ilka Mueller,1 Florian Lang,1 and Erich Gulbins2,*

Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,2 and Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany1

Received 6 October 2000/Returned for modification 9 November 2000/Accepted 8 January 2001

Pseudomonas aeruginosa, a gram-negative facultative pathogen, causes severe infections in immunocompromised and cystic fibrosis patients. However, the molecular details of the interaction between P. aeruginosa and mammalian cells are still largely unknown. Here we demonstrate that infection of human conjunctiva epithelial Chang cells with the well-characterized P. aeruginosa strain PAO-I results in rapid induction of apoptosis. Apoptosis was mediated by mitochondrial alterations, in particular mitochondrial depolarization, synthesis of reactive oxygen intermediates, and release of cytochrome c, as well as an activation of Jun N-terminal kinases (JNK). Stimulation of these events was dependent on upregulation of CD95 on infected cells, and a deficiency of CD95 or the CD95 ligand prevented mitochondrial changes, JNK activation, and apoptosis upon infection. Further, efficient apoptosis of Chang epithelial cells required infection with live P. aeruginosa, adhesion but not invasion of the bacteria, and expression of the type III secretion system in PAO-I. The data indicate a type III secretion system-dependent, sequential activation of several signaling pathways by P. aeruginosa PAO-I, resulting in apoptosis of the infected cell.

* Corresponding author. Mailing address: Dept. of Immunology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105. Phone: (901) 485-3085. Fax: (901) 495-3107. E-mail: erich.gulbins{at}stjude.org.

Infection and Immunity, April 2001, p. 2675-2683, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2675-2683.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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