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Ubiquitin and ubiquitin‐modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU
Author(s) -
Anderson David M.,
Schmalzer Katherine M.,
Sato Hiromi,
Casey Monika,
Terhune Scott S.,
Haas Arthur L.,
Feix Jimmy B.,
Frank Dara W.
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2011.07904.x
Subject(s) - biology , ubiquitin , effector , pseudomonas aeruginosa , type three secretion system , activator (genetics) , phospholipase , microbiology and biotechnology , biochemistry , enzyme , virulence , gene , bacteria , genetics
Summary 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.