title: Ubiquitin and ubiquitin-modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU.
abstract: 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.
authors: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors: David M
authors: DM
authors: Anderson
authors: Katherine M
authors: KM
authors: Schmalzer
authors: Hiromi
authors: H
authors: Sato
authors: Monika
authors: M
authors: Casey
authors: Scott S
authors: SS
authors: Terhune
authors: Arthur L
authors: AL
authors: Haas
authors: Jimmy B
authors: JB
authors: Feix
authors: Dara W
authors: DW
authors: Frank
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D002417:Cattle; D002460:Cell Line; D020536:Enzyme Activators / Q000378:metabolism*; D006801:Humans; D007956:Leukocidins / Q000235:genetics / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D020536:Enzyme Activators; D007956:Leukocidins; C510238:Pseudomonas aeruginosa Cytotoxins; C000606290:SOD1 protein, human; D025801:Ubiquitin; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1