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Article
Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
Journal of Cell Biology
  • Stefan A. Paschen, Technische Universität München
  • Jan G. Christian, Technische Universität München
  • Juliane Vier, Technische Universität München
  • Franziska Schmidt, Technische Universität München
  • Axel Walch, German Research Center for Environmental Health
  • David M. Ojcius, University of California, Merced
  • Georg Hacker, University Medical Centre Freiburg
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1083/jcb.200804023
Publication Date
7-14-2008
Abstract

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.

Citation Information
Stefan A. Paschen, Jan G. Christian, Juliane Vier, Franziska Schmidt, et al.. "Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease" Journal of Cell Biology Vol. 182 Iss. 1 (2008) p. 117 - 127 ISSN: 0021-9525
Available at: http://works.bepress.com/david-ojcius/79/