Host susceptibility to bacterial infection is influenced by a complex interaction of pathogen- and host-derived molecules. Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes a substantial number of clinically relevant, hospital-acquired infections. Many bacterial genes thought to contribute to its pathogenesis are regulated by the bacterial protein N-3-oxododecanoyl homoserine lactone (3OC12-HSL), which is degraded by a conserved family of host enzymes known as paraoxonases (PONs). The ability of PONs to degrade 3OC12-HSL suggests that PONs may offer protection against bacterial-induced pathology; however, this hypothesis has not been tested due to the complexity of generating a knockout model lacking all PON family members.
A recent report from Stoltz et al. exploits the fact that Drosophila lack all PON proteins to test the protective potential of PONs in this model organism. They found that expression of an activated form of PON1 protected flies against the toxicity of P. aeruginosa infection and promoted host survival. The protective effect of PON1 was dependent on its ability to inactivate 3OC12-HSL. This work provides insight into pathogen-host interactions and suggests that therapeutic induction of PON activity could have beneficial effects for infected patients.
