The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence.
Journal Article (Journal Article)
The obligate intracellular bacterial pathogen Chlamydia trachomatis injects numerous effector proteins into the epithelial cell cytoplasm to manipulate host functions important for bacterial survival. In addition, the bacterium secretes a serine protease, chlamydial protease-like activity factor (CPAF). Although several CPAF targets are reported, the significance of CPAF-mediated proteolysis is unclear due to the lack of specific CPAF inhibitors and the diversity of host targets. We report that CPAF also targets chlamydial effectors secreted early during the establishment of the pathogen-containing vacuole ("inclusion"). We designed a cell-permeable CPAF-specific inhibitory peptide and used it to determine that CPAF prevents superinfection by degrading early Chlamydia effectors translocated during entry into a preinfected cell. Prolonged CPAF inhibition leads to loss of inclusion integrity and caspase-1-dependent death of infected epithelial cells. Thus, CPAF functions in niche protection, inclusion integrity and pathogen survival, making the development of CPAF-specific protease inhibitors an attractive antichlamydial therapeutic strategy.
Full Text
Duke Authors
Cited Authors
- Jorgensen, I; Bednar, MM; Amin, V; Davis, BK; Ting, JPY; McCafferty, DG; Valdivia, RH
Published Date
- July 21, 2011
Published In
Volume / Issue
- 10 / 1
Start / End Page
- 21 - 32
PubMed ID
- 21767809
Pubmed Central ID
- PMC3147293
Electronic International Standard Serial Number (EISSN)
- 1934-6069
Digital Object Identifier (DOI)
- 10.1016/j.chom.2011.06.008
Language
- eng
Conference Location
- United States