| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Internal Medicine, University of Iowa, Iowa City, Iowa, United States
2 Iowa City, Iowa, United States; Internal Medicine, University of Iowa, Iowa City, Iowa, United States
3 Medicine, University of California, Los Angeles, California, United States
4 Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, United States
5 Medicine and Molecular & Medical Pharmacology, UCLA, Los Angeles, California, United States
6 Medicine, UCLA, Los Angeles, California, United States
7 Molecular and Medical Pharmacology, University of California, Los Angeles, California, United States
8 Microbiology, University of Washington, Seattle, Washington, United States
* To whom correspondence should be addressed. E-mail: joseph-zabner{at}uiowa.edu.
Pseudomonas aeruginosa is an important cause of nosocomial infections and is frequently present in the airways of cystic fibrosis patients. Quorum sensing mediates P. aeruginosa's virulence and biofilm formation through density-dependent interbacterial signaling with autoinducers. N-3-oxododecanoyl homoserine lactone (3OC12-HSL) is the major autoinducer in P. aeruginosa. We have previously shown that human airway epithelia and paraoxonases (PONs) degrade 3OC12-HSL. This study investigated the role of PON1, PON2, and PON3 in airway epithelial cell inactivation of 3OC12-HSL. All three PONs were present in murine tracheal epithelial cells, with PON2 and PON3 expressed at the highest levels. Lysates of tracheal epithelial cells from PON2 knockout mice, but not PON1 or PON3 knockout mice, had impaired 3OC12-HSL inactivation compared to wild type mice. In contrast, PON1, PON2, or PON3 targeted deletions did not affect 3OC12-HSL degradation by intact epithelia. Overexpression of PON2 enhanced 3OC12-HSL degradation by human airway epithelial cell lysates, but not by intact epithelia. Finally, using a quorum-sensing reporter strain of P. aeruginosa, we found that quorum sensing was enhanced in PON2 deficient airway epithelia. In summary, these results show that loss of PON2 impairs 3OC12-HSL degradation by airway epithelial cells and suggests that diffusion of 3OC12-HSL into the airway cells can be the rate-limiting step for degradation of the molecule.
This article has been cited by other articles:
|
|
 |
|
  R. Popat, S. A. Crusz, and S. P. Diggle The social behaviours of bacterial pathogens Br. Med. Bull., September 1, 2008; 87(1): 63 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Teiber, S. Horke, D. C. Haines, P. K. Chowdhary, J. Xiao, G. L. Kramer, R. W. Haley, and D. I. Draganov Dominant Role of Paraoxonases in Inactivation of the Pseudomonas aeruginosa Quorum-Sensing Signal N-(3-Oxododecanoyl)-L-Homoserine Lactone Infect. Immun., June 1, 2008; 76(6): 2512 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Williams Quorum sensing, communication and cross-kingdom signalling in the bacterial world Microbiology, December 1, 2007; 153(12): 3923 - 3938. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
