Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR, which contains RpfF interaction (FI)-Per/Arnt/Sim (PAS)-GGDEF-EAL domains, controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid (C12:0) and oleic acid (C18:1), respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. It was revealed that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. The BDSF-binding site are distinct from the substrate binding site of DsfR. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of the fatty acyl-CoA ligase DsfR that control bacterial virulence as a response regulator of QS signal.
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