Abstract
SUMMARYDiffusible 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 thatcis-2-decenoic acid (cis-DA) is involved in modulation of biofilm dispersion inPseudomonas aeruginosa, but its signaling mechanism remains vague. Here, we report thatcis-DA regulates the physiology and virulence ofP. aeruginosathrough 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 oflasR. Further analysis showed that the FadD1 is a response regulator ofcis-DA with a DNA-binding leucine zipper motif to control the transcription of various target genes. Moreover, FadD1 exhibited catalytic activity oncis-2-dodecenoic acid (BDSF) ofBurkholderia cenocepaciaand enhanced the competitiveness ofP. 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 FigureHighlightsThe long-chain fatty acid-CoA ligase FadD1 acts as a global transcriptional regulator inP. aeruginosa. FadD1 is a receptor of QS signalcis-DA and functions at the top of the QS hierarchy inP. aeruginosa. The homolog of FadD1 inP. fluorescenscould bind to the target gene promoter by responding tocis-DA.In briefPseudomonas aeruginosais 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 employscis-2-decenoic acid (cis-DA) quorum sensing to regulate the physiology and pathogenesis. Songet al.demonstrate that the long-chain fatty acid-CoA ligase FadD1 controls the important biological functions and virulence inP. aeruginosaas a novel response regulator ofcis-DA signal.
Publisher
Cold Spring Harbor Laboratory