The attenuated virulence of a B urkholderia cenocepacia paaABCDE mutant is due to inhibition of quorum sensing by release of phenylacetic acid

Summary The phenylacetic acid degradation pathway of B urkholderia cenocepacia is active during cystic fibrosis‐like conditions and is necessary for full pathogenicity of B . cenocepacia in nematode and rat infection models; however, the reasons for such requirements are unknown. Here, we show that the attenuated virulence of a phenylacetic acid catabolism mutant is due to quorum sensing inhibition. Unlike wild‐type B . cenocepacia , a deletion mutant of the phenylacetyl‐ CoA monooxygenase complex (Δ paaABCDE ) released phenylacetic acid in the medium that favours infection in C aenorhabditis elegans . Addition of phenylacetic acid further decreased the pathogenicity of the Δ paaABCDE , which cannot metabolize phenylacetic acid, but did not affect the wild‐type, due to phenylacetic acid consumption. In line with reduced detection of acyl‐homoserine lactones in spent medium, the Δ paaABCDE exhibited transcriptional inhibition of the quorum sensing system cepIR . Phenotypes repressed in Δ paaABCDE , protease activity and pathogenicity against C . elegans , increased with exogenous N ‐octanoyl‐L‐homoserine lactone. Thus, we demonstrate that the attenuated phenotype of B . cenocepacia Δ paaABCDE is due to quorum sensing inhibition by release of phenylacetic acid, affecting N ‐octanoyl‐L‐homoserine lactone signalling. Further, we propose that active degradation of phenylacetic acid by B . cenocepacia during growth in cystic fibrosis‐like conditions prevents accumulation of a quorum sensing inhibiting compound.