title: The attenuated virulence of a Burkholderia cenocepacia paaABCDE mutant is due to inhibition of quorum sensing by release of phenylacetic acid.
abstract: The phenylacetic acid degradation pathway of Burkholderia 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 (ΔpaaABCDE) released phenylacetic acid in the medium that favours infection in Caenorhabditis elegans. Addition of phenylacetic acid further decreased the pathogenicity of the ΔpaaABCDE, 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 ΔpaaABCDE exhibited transcriptional inhibition of the quorum sensing system cepIR. Phenotypes repressed in ΔpaaABCDE, 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 ΔpaaABCDE 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.
authors.affiliation: Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Pribytkova
authors.forename: Tasia Joy
authors.initials: TJ
authors.lastname: Lightly
authors.forename: Brijesh
authors.initials: B
authors.lastname: Kumar
authors.forename: Steve P
authors.initials: SP
authors.lastname: Bernier
authors.forename: John L
authors.initials: JL
authors.lastname: Sorensen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
authors.forename: Silvia T
authors.initials: ST
authors.lastname: Cardona
mesh_terms: D054742:Acyl-Butyrolactones / Q000032:analysis; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D019121:Burkholderia Infections / Q000382:microbiology / Q000473:pathology; D057508:Burkholderia cenocepacia / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D017173:Caenorhabditis elegans; D004195:Disease Models, Animal; D017353:Gene Deletion; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010648:Phenylacetates / Q000378:metabolism*; D053038:Quorum Sensing / Q000187:drug effects*; D014774:Virulence
chemical_list: D054742:Acyl-Butyrolactones; D001426:Bacterial Proteins; D010648:Phenylacetates; C025136:phenylacetic acid