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Pseudomonas aeruginosa type III-secreted toxin ExoT inhibits host-cell division by targeting cytokinesis at multiple

Sasha H Shafikhani1, Joanne Engel

  • 1Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94143, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 13, 2006
PubMed

Insights

Pseudomonas aeruginosa infection hinders mammalian cell division (cytokinesis) using its type III secretion system and exotoxin T (ExoT). ExoT

Area of Science:

  • Microbiology
  • Cell Biology
  • Pathogenesis

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen requiring epithelial injury for infection.
  • Bacterial pathogens can manipulate host cell processes to facilitate infection.

Purpose of the Study:

  • To investigate the mechanism by which Pseudomonas aeruginosa inhibits mammalian cytokinesis.
  • To determine the role of the type III secretion system and exotoxin T (ExoT) in this inhibition.

Main Methods:

  • Investigated the role of type III secretion system and exotoxin T (ExoT) in P. aeruginosa-mediated inhibition of cytokinesis.
  • Analyzed the distinct roles of ExoT's GTPase-activating protein (GAP) and ADP-ribosyl transferase (ADPRT) domains.

Main Results:

  • P. aeruginosa inhibits mammalian cytokinesis in a type III secretion system and ExoT-dependent manner.
  • ExoT's GAP domain inhibits early cytokinesis steps via RhoA inhibition.
  • ExoT's ADPRT domain inhibits late cytokinesis steps by blocking syntaxin-2 midbody localization.

Conclusions:

  • Pseudomonas aeruginosa utilizes exotoxin T to disrupt host cell division.
  • ExoT employs distinct mechanisms via its two domains to block cytokinesis at different stages.
  • This study reveals a novel bacterial strategy targeting host cell cytokinesis.

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