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Paschen, S.A.* ; Christian, J.G. ; Vier, J.* ; Schmidt, F. ; Walch, A.K. ; Ojcius, D.M.* ; Häcker, G.*

Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease.

J. Cell Biol. 182, 117-127 (2008)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Chlamydiae replicate in a vacuole within epithelial cells and commonly induce cell damage and a deleterious inflammatory response of unknown molecular pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates from the vacuole to the cytosol, where it cleaves several cellular proteins. CPAF is synthesized as an inactive precursor that is processed and activated during infection. Here, we show that CPAF can be activated in uninfected cells by experimentally induced oligomerization, reminiscent of the activation mode of initiator caspases. CPAF activity induces proteolysis of cellular substrates including two novel targets, cyclin B1 and PARP, and indirectly results in the processing of pro-apoptotic BH3-only proteins. CPAF activation induces striking morphological changes in the cell and, later, cell death. Biochemical and ultrastructural analysis of the cell death pathway identify the mechanism of cell death as nonapoptotic. Active CPAF in uninfected human cells thus mimics many features of chlamydial infection, implicating CPAF as a major factor of chlamydial pathogenicity, Chlamydia-associated cell damage, and inflammation.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0021-9525
e-ISSN 1540-8140
Journal Journal of Cell Biology, The
Quellenangaben Volume: 182, Issue: 1, Pages: 117-127 Article Number: , Supplement: ,
Publisher Rockefeller University Press
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)