The long-chain fatty acid-CoA ligase FadD1 monitorsPseudomonas aeruginosaquorum sensing as a receptor of cis-2-decenoic acid

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SUMMARY Diffusible signal factor (DSF)-family quorum sensing (QS) signals are widely utilized by many bacterial pathogens to modulate various biological functions and virulence. Previous studies showed that cis -2-decenoic acid ( cis -DA) is involved in modulation of biofilm dispersion in Pseudomonas aeruginosa , but its signaling mechanism remains vague. Here, we report that cis -DA regulates the physiology and virulence of P. aeruginosa through the long-chain fatty acid-CoA ligase FadD1. Cis -DA specifically binds to FadD1 with high affinity and enhances the binding of FadD1 to the promoter DNA region of lasR . Further analysis showed that the FadD1 is a response regulator of cis -DA with a DNA-binding leucine zipper motif to control the transcription of various target genes. Moreover, FadD1 exhibited 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, which is highlighted by its receptor and response regulator evolved from a canonical enzyme of fatty acid metabolism. Abstract Figure Highlights The long-chain fatty acid-CoA ligase FadD1 acts as a global transcriptional regulator in P. aeruginosa . FadD1 is a receptor of QS signal cis -DA and functions at the top of the QS hierarchy in P. aeruginosa . The homolog of FadD1 in P. fluorescens could bind to the target gene promoter by responding to cis -DA. In brief Pseudomonas aeruginosa is a human pathogen with antibiotic resistance and a wide range of dynamic defenses makes it an extremely challenging organism to treat in modern-day medicine. It employs cis -2-decenoic acid ( cis -DA) quorum sensing to regulate the physiology and pathogenesis. Song et al. demonstrate that the long-chain fatty acid-CoA ligase FadD1 controls the important biological functions and virulence in P. aeruginosa as a novel response regulator of cis -DA signal.