title: Pseudomonas aeruginosa type III-secreted toxin ExoT inhibits host-cell division by targeting cytokinesis at multiple steps.
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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94143, USA.
authors.forename: Sasha H
authors.initials: SH
authors.lastname: Shafikhani
authors.forename: Joanne
authors.initials: J
authors.lastname: Engel
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D002460:Cell Line; D048749:Cytokinesis / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; C477521:ExoT protein, Pseudomonas aeruginosa; D020690:GTPase-Activating Proteins; D050827:Syntaxin 1; D036002:ADP Ribose Transferases