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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

172 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalFEMS Microbiology Letters
Issue number1
StatePublished - Dec 1 2005


  • Innate immunity
  • Paraoxonase
  • Pseudomonas aeruginosa
  • Quorum-sensing

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology
  • Genetics


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