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Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens
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The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote

Ine Jorgensen1, Maria M Bednar, Vishar Amin

  • 1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.

Cell Host & Microbe
|July 20, 2011
PubMed

Insights

Chlamydia trachomatis protease (CPAF) degrades early bacterial effectors, preventing reinfection and maintaining the pathogen's niche. Inhibiting CPAF disrupts inclusion integrity and causes cell death, highlighting CPAF as a therapeutic target.

Area of Science:

  • Microbiology
  • Cell Biology
  • Protease Function

Background:

  • Chlamydia trachomatis is an obligate intracellular bacterium that manipulates host cells using effector proteins.
  • The secreted serine protease, chlamydial protease-like activity factor (CPAF), has known targets, but its precise role is unclear.
  • Lack of specific CPAF inhibitors and diverse host targets have limited understanding of CPAF's significance.

Purpose of the Study:

  • To investigate the role of CPAF in targeting early bacterial effectors.
  • To determine the function of CPAF in preventing superinfection and maintaining inclusion integrity.
  • To evaluate CPAF as a potential therapeutic target for Chlamydia infections.

Main Methods:

  • Design and utilization of a cell-permeable, CPAF-specific inhibitory peptide.
  • Analysis of CPAF's effect on early Chlamydia effectors translocated into host cells.
  • Assessment of inclusion integrity and host cell viability upon CPAF inhibition.

Main Results:

  • CPAF was found to target and degrade early Chlamydia effectors during inclusion establishment.
  • CPAF inhibition prevented superinfection by blocking the degradation of these early effectors.
  • Prolonged CPAF inhibition led to loss of inclusion integrity and caspase-1-dependent host cell death.

Conclusions:

  • CPAF plays a critical role in protecting the Chlamydia niche and ensuring pathogen survival.
  • CPAF's functions include maintaining inclusion integrity and preventing superinfection.
  • Developing specific CPAF protease inhibitors presents a promising antichlamydial therapeutic strategy.

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