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Published online 27 September 2004 doi:10.1084/jem.20040402
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 7, 905-916
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*Chlamydia Infections
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Chlamydia Inhibit Host Cell Apoptosis by Degradation of Proapoptotic BH3-only Proteins

Silke F. Fischer1, Juliane Vier1, Susanne Kirschnek1, Andreas Klos2, Simone Hess2, Songmin Ying1, and Georg Häcker1

1 Institute for Medical Microbiology, Technische Universität München, D-81675 Munich, Germany
2 Medical Microbiology, Medical School Hannover, D-30623 Hanover, Germany

Address correspondence to Georg Häcker, Institute for Medical Microbiology, Technische Universität München, Trogerstr. 9, D-81675 Munich, Germany. Phone: 49-89-4140-4121; Fax: 49-89-4140-4868; email: hacker{at}lrz.tum.de

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.

Key Words: bacteria • pathogens • cell death • proteasome • mitochondria

Abbreviations used in this paper: CPAF, chlamydial proteasome-like activity factor; EGFP, enhanced GFP; MOI, multiplicity of infection.


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