Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing

Egon A Ozer; Alejandro Pezzulo; Diana M Shih; Carlene Chun; Clement Furlong; Aldons J Lusis; Everett P Greenberg; Joseph Zabner

doi:10.1016/j.femsle.2005.09.023

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Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing

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Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing

Egon A Ozer, Alejandro Pezzulo, Diana M Shih, Carlene Chun, Clement Furlong, Aldons J Lusis, Everett P Greenberg and Joseph Zabner

FEMS microbiology letters, Vol.253(1), pp.29-37

2005

DOI: 10.1016/j.femsle.2005.09.023

PMID: 16260097

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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.

Pseudomonas aeruginosa

Innate immunity

Quorum-sensing

Paraoxonase

Details

Title: Subtitle: Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing
Creators: Egon A Ozer - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
Alejandro Pezzulo - Universidad Central de Venezuela, Caracas, Venezuela
Diana M Shih - Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, United States
Carlene Chun - Department of Medical Microbiology, University of Wisconsin-Madison, Madison, WI 53706, United States
Clement Furlong - Department of Medical Genetics, University of Washington, Seattle, WA 98195, United States
Aldons J Lusis - Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, United States
Everett P Greenberg - Department of Microbiology, University of Iowa, Iowa City, IA 52242, United States
Joseph Zabner - Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: FEMS microbiology letters, Vol.253(1), pp.29-37
DOI: 10.1016/j.femsle.2005.09.023
PMID: 16260097
NLM abbreviation: FEMS Microbiol Lett
ISSN: 0378-1097
eISSN: 1574-6968
Publisher: Elsevier B.V
Language: English
Date published: 2005
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Internal Medicine
Record Identifier: 9984094567602771

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