Paraoxonases, Quorum Sensing, And Pseudomonas Aeruginosa

Abstract

Pseudomonas aeruginosa is a major cause of pulmonary infections in hospitalized, immunocompromised, and chronic lung disease patients, such as those with cystic fibrosis (CF). CF affects multiple organ systems, but infection in the airways is the most important clinical problem and the primary cause of death. P. aeruginosa can coordinate its activities and behave as a group through a population-dependent process termed quorum sensing. P. aeruginosa uses N-acyl homoserine lactone (AHL) quorum-sensing molecules to regulate the expression of genes implicated in bacterial virulence and biofilm formation. AHLs produced and recognized by P. aeruginosa include N-3-oxododecanoyl homoserine lactone (3OC12-HSL) and N-butanoyl homoserine lactone (C4-HSL). Certain molecules and bacterial lactonases have been identified that degrade or compete with quorum-sensing signals and alter the pathogenesis of Gram-negative organisms, including P. aeruginosa. We have found that paraoxonases (PONs) present in airway epithelial cells and serum can inactivate 3OC12-HSL’s biological activity by hydrolyzing its lactone ring (lactonase activity). Of clinical interest, we have also shown that PON1 can inhibit P. aeruginosa biofilm formation. Finally, based upon studies using airway cells from PON2-deficient mice, we have demonstrated that PON2 is required for airway epithelia inactivation of 3OC12-HSL. These findings suggest that PONs may represent a novel component of the innate immune system designed to interfere with P. aeruginosa quorum-sensing control