Cis-2-decenoic acid modulates Pseudomonas aeruginosa virulence through a noncanonical transcriptional regulator.

Diffusible signal factor (DSF)-family quorum sensing (QS) signals are widely utilized by many pathogenic bacteria to modulate various biological functions and virulence. Previous studies showed that cis-2-decenoic acid (cis-DA) is involved in the modulation of biofilm dispersion in Pseudomonas aeruginosa, but the regulatory mechanism is unclear. Here, we report that cis-DA regulates the physiology and virulence of P. aeruginosa through FadD1, a long-chain fatty acid-CoA ligase. cis-DA specifically binds to FadD1 and enhances the binding ability of FadD1 to the target gene promoter DNA regions. Further analysis showed that FadD1 is a global regulatory factor that controls the transcription of various target genes. Moreover, FadD1 showed catalytic activity on cis-2-dodecenoic acid (BDSF) of Burkholderia cenocepacia and enhanced the competitiveness of P. aeruginosa. Together, our work presents a new DSF-type QS signaling system in P. aeruginosa, which is highlighted by the signal receptor evolved from a canonical enzyme of fatty acid metabolism.