Pseudomonas aeruginosa-induced apoptosis involves mitochondria and stress-activated protein kinases.
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.
Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany.
V
V
Jendrossek
H
H
Grassmé
I
I
Mueller
F
F
Lang
E
E
Gulbins
D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000494:pharmacology; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D048031:JNK Mitogen-Activated Protein Kinases; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008928:Mitochondria / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D017382:Reactive Oxygen Species; D019014:fas Receptor / Q000502:physiology
D001426:Bacterial Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D019014:fas Receptor; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases