<i>Chlamydia</i> Inhibit Host Cell Apoptosis by Degradation of Proapoptotic BH3-only Proteins
-
- Silke F. Fischer
- 1Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany
-
- Juliane Vier
- 1Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany
-
- Susanne Kirschnek
- 1Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany
-
- Andreas Klos
- 2Medical Microbiology, Medical School Hannover, D-30623 Hanover, Germany
-
- Simone Hess
- 2Medical Microbiology, Medical School Hannover, D-30623 Hanover, Germany
-
- Songmin Ying
- 1Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany
-
- Georg Häcker
- 1Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany
この論文をさがす
説明
<jats:p>Chlamydia are obligate intracellular bacteria that replicate in a vacuole inside a host cell. Chlamydial infection has been shown to protect the host cell against apoptotic stimuli. This is likely important for the ability of Chlamydia to reproduce in human cells. Here we show that resistance to apoptosis is conveyed by the destruction of the proapoptotic BH3-only proteins Bim/Bod, Puma, and Bad during infection. Apoptotic stimuli were blocked upstream of the mitochondrial activation of Bax/Bak. During infection with both species, Chlamydia trachomatis and Chlamydia pneumoniae, Bim protein gradually disappeared without noticeable changes in Bim mRNA. The disappearance was blocked by inhibitors of the proteasome. Infected cells retained sensitivity to Bim expressed by transfection, indicating functional relevance of the Bim disappearance. Fusion to Bim targeted the green fluorescent protein for destruction during infection. Analysis of truncation mutants showed that a short region of Bim containing the BH3 domain was sufficient for destruction during chlamydial infection. Like Bim, Puma and Bad proteins disappeared during infection. These results reveal a novel way by which microbes can interfere with the host cell's apoptotic machinery, and provide a molecular explanation of the cellular resistance to apoptosis during infection with Chlamydia.</jats:p>
収録刊行物
-
- The Journal of Experimental Medicine
-
The Journal of Experimental Medicine 200 (7), 905-916, 2004-09-27
Rockefeller University Press