Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing |
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Authors: | Ozer Egon A Pezzulo Alejandro Shih Diana M Chun Carlene Furlong Clement Lusis Aldons J Greenberg Everett P Zabner Joseph |
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Affiliation: | Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. |
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Abstract: | The pathogenic bacterium Pseudomonas aeruginosa uses acyl-HSL quorum-sensing signals to regulate genes controlling virulence and biofilm formation. We found that paraoxonase 1 (PON1), a mammalian lactonase with an unknown natural substrate, hydrolyzed the P. aeruginosa acyl-HSL 3OC12-HSL. In in vitro assays, mouse serum-PON1 was required and sufficient to degrade 3OC12-HSL. Furthermore, PON2 and PON3 also degraded 3OC12-HSL effectively. Serum-PON1 prevented P. aeruginosa quorum-sensing and biofilm formation in vitro by inactivating the quorum-sensing signal. Although 3OC12-HSL production by P. aeruginosa was important for virulence in a mouse sepsis model, Pon1-knock-out mice were paradoxically protected. These mice showed increased levels of PON2 and PON3 mRNA in epithelial tissues suggesting a possible compensatory mechanism. Thus, paraoxonase interruption of bacterial communication represents a novel mechanism to modulate quorum-sensing by bacteria. The consequences for host immunity are yet to be determined. |
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Keywords: | Pseudomonas aeruginosa Quorum-sensing Paraoxonase Innate immunity |
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