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Pseudomonas aeruginosa-induced apoptosis involves mitochondria and stress-activated protein kinases
V Jendrossek1, H Grassmé, I Mueller
1Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany.
Abstract:
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.
Insights
Pseudomonas aeruginosa infection triggers programmed cell death (apoptosis) in human epithelial cells. This process involves mitochondrial damage and specific signaling pathways, requiring bacterial adhesion and type III secretion.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen causing severe infections.
- The molecular mechanisms underlying P. aeruginosa interactions with host cells remain poorly understood.
Purpose of the Study:
- To elucidate the molecular pathways involved in P. aeruginosa-induced apoptosis in human epithelial cells.
Main Methods:
- Infection of human conjunctiva epithelial Chang cells with P. aeruginosa strain PAO-I.
- Analysis of apoptosis markers, mitochondrial function, and signaling pathway activation (e.g., JNK).
- Investigation of the role of CD95, CD95 ligand, bacterial adhesion, invasion, and type III secretion system.
Main Results:
- P. aeruginosa PAO-I infection rapidly induces apoptosis in Chang cells.
- Apoptosis is mediated by mitochondrial depolarization, reactive oxygen species production, cytochrome c release, and JNK activation.
- These events are dependent on CD95 upregulation and require live bacteria, adhesion, and the type III secretion system.
Conclusions:
- P. aeruginosa utilizes its type III secretion system to sequentially activate host cell signaling pathways, leading to apoptosis.
- Bacterial adhesion, but not invasion, is crucial for initiating this apoptotic response.