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Ubiquitin and ubiquitin-modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU.
Mol Microbiol. 2011 Dec; 82(6):1454-67
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30 Jan 2012
Virginia Miller
F1000 Microbiology
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
F1000 Microbiology
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
New Finding
DOI: 10.3410/f.13480966.14859118
This beautifully conducted study not only provides an explanation for the previously controversial observation that yeast SOD1 (superoxide dismutase 1) activates the type III secretion effector, ExoU, of Pseudomonas, it also demonstrates a novel way in which a pathogen uses the eukaryotic ubiquitin system for its own purposes.
ExoU had previously been shown to have phospholipase activity, but only in the presence of a eukaryotic cofactor such as SOD1. Here, it is shown that it is not specifically SOD1, but rather ubiquitin (or ubiquitylated proteins such as SOD1) that serve as the cofactor. The lack of ubiquitin in the bacterial cell protects Pseudomonas from the action of ExoU but makes the host cell exquisitely sensitive. This is the first description of a bacterial enzyme using ubitquitin as an activator.
Disclosures
None declared
Add Comment
Miller V: F1000Prime Recommendation of [Anderson DM et al., Mol Microbiol 2011, 82(6):1454-67]. In F1000Prime, 30 Jan 2012; DOI: 10.3410/f.13480966.14859118. F1000Prime.com/13480966#eval14859118
F1000Prime Recommendations, Dissents and Comments for [Anderson DM et al., Mol Microbiol 2011, 82(6):1454-67]. In F1000Prime, 18 Jun 2013; F1000Prime.com/13480966
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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.
© 2011 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2011.07904.x
PMID: 22040088
