Ubiquitin and ubiquitin-modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU. Mol Microbiol 2011 Dec;82(6):1454-67
Date
11/02/2011Pubmed ID
22040088Pubmed Central ID
PMC3237844DOI
10.1111/j.1365-2958.2011.07904.xScopus ID
2-s2.0-83355166268 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that possesses a type III secretion system (T3SS) critical for evading innate immunity and establishing acute infections in compromised patients. Our research has focused on the structure-activity relationships of ExoU, the most toxic and destructive type III effector produced by P. aeruginosa. ExoU possesses phospholipase activity, which is detectable in vitro only when a eukaryotic cofactor is provided with membrane substrates. We report here that a subpopulation of ubiquitylated yeast SOD1 and other ubiquitylated mammalian proteins activate ExoU. Phospholipase activity was detected using purified ubiquitin of various chain lengths and linkage types; however, free monoubiquitin is sufficient in a genetically engineered dual expression system. The use of ubiquitin by a bacterial enzyme as an activator is unprecedented and represents a new aspect in the manipulation of the eukaryotic ubiquitin system to facilitate bacterial replication and dissemination.
Author List
Anderson DM, Schmalzer KM, Sato H, Casey M, Terhune SS, Haas AL, Feix JB, Frank DWAuthors
Jimmy B. Feix PhD Professor in the Biophysics department at Medical College of WisconsinDara W. Frank PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Scott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBacterial Proteins
Bacterial Secretion Systems
Cattle
Cell Line
Enzyme Activators
Humans
Leukocidins
Pseudomonas Infections
Pseudomonas aeruginosa
Superoxide Dismutase
Superoxide Dismutase-1
Ubiquitin