<i>Cis</i> ‐2‐decenoic acid modulates <i>Pseudomonas aeruginosa</i> 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 <i>cis</i>-2-decenoic acid (<i>cis</i>-DA) is involved in the modulation of biofilm dispersion in <i>Pseudomonas aeruginosa</i>, but the regulatory mechanism is unclear. Here, we report that <i>cis</i>-DA regulates the physiology and virulence of <i>P. aeruginosa</i> through FadD1, a long-chain fatty acid-CoA ligase. <i>cis</i>-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 <i>cis</i>-2-dodecenoic acid (BDSF) of <i>Burkholderia cenocepacia</i> and enhanced the competitiveness of <i>P. aeruginosa</i>. Together, our work presents a new DSF-type QS signaling system in <i>P. aeruginosa</i>, which is highlighted by the signal receptor evolved from a canonical enzyme of fatty acid metabolism.