A Chlamydial Plasmid-Dependent Secretion System for the Delivery of Virulence Factors to the Host Cytosol

Lei Lei1, Chunfu Yang1, Michael John Patton1

  • 1Chlamydial Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Mbio
|June 8, 2021
PubMed

Insights

Chlamydia bacteria use a novel plasmid-dependent system to secrete virulence factors. This system involves unique globular structures that export key proteins from the inclusion to the host cell cytosol.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Cell Biology

Background:

  • Chlamydia are obligate intracellular bacteria with a unique developmental cycle.
  • The chlamydial plasmid is crucial for virulence, regulating key factors like Pgp3 and GlgA.
  • The mechanism for secreting these factors from the inclusion to the host cytosol was previously unknown.

Purpose of the Study:

  • To identify and characterize the novel secretion system responsible for delivering chlamydial virulence factors to the host cytosol.
  • To elucidate the role of plasmid gene protein 4 (Pgp4) in this secretion process.

Main Methods:

  • Identification of globular structures originating from reticulate bodies.
  • Analysis of protein content within these structures, including Pgp4-regulated proteins.
  • Genetic manipulation to assess the necessity of Pgp4 for structure formation and secretion.
  • Comparison with known type 2 and type 3 secretion systems.
  • Characterization of globular structures using markers like lipopolysaccharide, outer membrane protein, and heat shock protein 60.

Main Results:

  • A novel plasmid-dependent secretion system was identified, utilizing distinct globular structures.
  • These structures, originating from midcycle reticulate bodies, contain virulence factors Pgp3 and GlgA, along with Pgp4-regulated proteins.
  • Pgp4 is essential for the formation of these globular structures and the subsequent secretion of Pgp3 and GlgA.
  • Secretion via these structures is independent of known chlamydial secretion systems (T2SS and T3SS).
  • Globular structures resemble outer membrane vesicles, enriched in lipopolysaccharide.

Conclusions:

  • A novel Pgp4-dependent secretion system, mediated by outer membrane vesicles, transports chlamydial virulence factors to the host cytosol.
  • This discovery provides a new understanding of Chlamydia pathogenesis and immune evasion strategies.
  • The identified system is critical for exporting plasmid-regulated virulence factors, impacting host-pathogen interactions.

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