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Modulation of host cell endocytosis by the type III cytotoxin, Pseudomonas ExoS

Qing Deng1, Joseph T Barbieri

  • 1Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.

Traffic (Copenhagen, Denmark)
|September 10, 2008
PubMed

Insights

Pseudomonas aeruginosa ExoS toxin uses its RhoGAP activity to block bacterial entry and its ADPr activity to disrupt vesicle transport, impacting epithelial cell function and bacterial virulence.

Area of Science:

  • Microbiology
  • Cell Biology
  • Toxicology

Background:

  • Pseudomonas aeruginosa utilizes type III secretion systems to deliver effector proteins like ExoS into host cells.
  • ExoS is a bifunctional toxin with Rho GTPase-activating protein (RhoGAP) and ADP-ribosyltransferase (ADPr) activities.

Purpose of the Study:

  • To investigate the distinct roles of ExoS's RhoGAP and ADPr activities in disrupting mammalian epithelial cell physiology.
  • To elucidate the specific cellular processes affected by each enzymatic activity of ExoS.

Main Methods:

  • Assessing bacterial internalization and phagocytosis in epithelial cells treated with ExoS variants.
  • Analyzing vesicle trafficking, including fluid-phase uptake and epidermal growth factor receptor (EGFR) degradation.
  • Investigating the localization of EGFR and its interaction with clathrin-coated vesicles (CCVs) and endosomes.
  • Identifying Rab proteins ADP-ribosylated by ExoS using biochemical assays.

Main Results:

  • ExoS's RhoGAP activity inhibited bacterial internalization, while its ADPr activity impaired vesicle trafficking.
  • ADPr activity prevented the maturation of CCVs into Rab5-positive early endosomes, affecting EGFR degradation.
  • ExoS's ADPr activity directly ADP-ribosylated Rab proteins, including Rab5 and Rab9, interfering with their function.

Conclusions:

  • The RhoGAP and ADPr activities of ExoS exert distinct effects on epithelial cells.
  • ExoS's ADPr activity inhibits mammalian vesicle trafficking, representing a novel bacterial toxin virulence mechanism.
  • Understanding these distinct functions provides insights into Pseudomonas aeruginosa pathogenesis.

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