Document Detail


The Chlamydia Protease CPAF Regulates Host and Bacterial Proteins to Maintain Pathogen Vacuole Integrity and Promote Virulence.
MedLine Citation:
PMID:  21767809     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Ine Jorgensen; Maria M Bednar; Vishar Amin; Beckley K Davis; Jenny P Y Ting; Dewey G McCafferty; Raphael H Valdivia
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell host & microbe     Volume:  10     ISSN:  1934-6069     ISO Abbreviation:  Cell Host Microbe     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101302316     Medline TA:  Cell Host Microbe     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-32     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
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