These authors contributed equally to this work.
Ubiquitin and ubiquitin-modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU
Article first published online: 21 NOV 2011
© 2011 Blackwell Publishing Ltd
Volume 82, Issue 6, pages 1454–1467, December 2011
How to Cite
Anderson, D. M., Schmalzer, K. M., Sato, H., Casey, M., Terhune, S. S., Haas, A. L., Feix, J. B. and Frank, D. W. (2011), Ubiquitin and ubiquitin-modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU. Molecular Microbiology, 82: 1454–1467. doi: 10.1111/j.1365-2958.2011.07904.x
- Issue published online: 9 DEC 2011
- Article first published online: 21 NOV 2011
- Accepted manuscript online: 31 OCT 2011 10:31AM EST
- Accepted 24 October, 2011.
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.