title: Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing.
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.
authors.affiliation: Department of Internal Medicine Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Egon A
authors.initials: EA
authors.lastname: Ozer
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pezzulo
authors.forename: Diana M
authors.initials: DM
authors.lastname: Shih
authors.forename: Carlene
authors.initials: C
authors.lastname: Chun
authors.forename: Clement
authors.initials: C
authors.lastname: Furlong
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Everett P
authors.initials: EP
authors.lastname: Greenberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D043303:Aryldialkylphosphatase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D005798:Genes, Bacterial; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000201:enzymology / Q000235:genetics / Q000382:microbiology; D011552:Pseudomonas Infections / Q000201:enzymology / Q000235:genetics / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity / Q000502:physiology; D018805:Sepsis / Q000201:enzymology / Q000235:genetics / Q000382:microbiology; D015398:Signal Transduction
chemical_list: C088386:homoserine lactone; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D015107:4-Butyrolactone