# Cis‐2‐decenoic acid modulates Pseudomonas aeruginosa virulence through a noncanonical transcriptional regulator

## TL;DR

This study shows how cis-2-decenoic acid affects Pseudomonas aeruginosa virulence by interacting with a specific enzyme, FadD1, which acts as a new type of signaling receptor.

## Contribution

The discovery that FadD1 functions as a noncanonical transcriptional regulator and QS signal receptor for cis-DA in Pseudomonas aeruginosa.

## Key findings

- cis-DA binds to FadD1, enhancing its DNA promoter binding and regulating virulence genes.
- FadD1 is a global regulator of QS systems and biofilm-related functions in P. aeruginosa.
- FadD1 also catalyzes cis-2-dodecenoic acid and enhances bacterial competitiveness.

## Abstract

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.

Quorum sensing (QS) is widely presented as an intercellular communication mechanism in bacteria. This study demonstrates that FadD1, a long‐chain fatty acid‐CoA ligase with a DNA‐binding leucine zipper motif, is a receptor of cis‐2‐decenoic acid (cis‐DA) in Pseudomonas aeruginosa. Perception of cis‐DA enhances the binding of FadD1 to the lasR promoter to control the rhl‐ and pqs‐QS systems. This study reveals a class of specific fatty acid‐CoA ligases with a leucine zipper motif as novel QS signal receptors, playing important roles in the virulence of bacteria.