Pseudomonas aeruginosa type III-secreted toxin ExoT inhibits host-cell division by targeting cytokinesis at multiple steps
- *Division of Infectious Diseases, Department of Medicine and
- †Department of Microbiology and Immunology, University of California, San Francisco, CA 94143
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Edited by E. Peter Greenberg, University of Washington School of Medicine, Seattle, WA, and approved August 31, 2006 (received for review July 14, 2006)
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that requires preexisiting epithelial injury to cause acute infections. We report that P. aeruginosa inhibits mammalian cytokinesis in a type III secretion system and exotoxin T (ExoT)-dependent manner. ExoT is a bifunctional type III secretion system effector protein that contains an N-terminal GTPase-activating protein domain and a C-terminal ADP-ribosyl transferase domain. Each of its domains inhibits cytokinesis in a kinetically, morphologically, and mechanistically distinct manner. The GTPase-activating protein-mediated inhibition of cytokinesis occurs early, likely as a consequence of its inhibitory effect on RhoA. The ADP-ribosyl transferase domain inhibits late steps of cytokinesis by blocking syntaxin-2 localization to the midbody, an event essential for completion of cytokinesis. These findings provide an example of a bacterial pathogen targeting cytokinesis.
Footnotes
- ‡To whom correspondence should be addressed. E-mail: jengel{at}medicine.ucsf.edu
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Author contributions: S.H.S. and J.E. designed research; S.H.S. performed research; S.H.S. and J.E. analyzed data; and S.H.S. and J.E. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS direct submission.
- Abbreviations:
- TTSS,
- type III secretion system;
- ΔU,
- PA103 ΔexoU;
- ΔUΔT,
- PA103 ΔexoU ΔexoT;
- GAP,
- GTPase-activating protein;
- ADPRT,
- ADP-ribosyl transferase;
- PI,
- propidium iodide;
- IF,
- immunofluorescent
- © 2006 by The National Academy of Sciences of the USA
