Background: Metabolic pathways are important in the modulation of quorum sensing (QS) system in Pseudomonas aeruginosa, providing potential targets for new therapeutics against QS-controlled virulence in lung infection. QscR is an anti-activator LuxR homologue that can delay the production of QS-controlled virulence by activating PA1895-1897 operon. We aimed to explore the underlying metabolic mechanism and its application in the anti-QS therapy.  
Methods: Metabolomics analyses were performed to identify critical metabolites regulated by PA1895-1897 operon. Time-course experiments were conducted to determine whether palmitoleic acid (PMA) participate in the delay of QS activation. Additionally, the effect of PMA on P. aeruginosa virulence was examined both in vitro and in vivo. 
Results: PA1895-1897 operon significantly up-regulated PMA synthesis. In time-course experiments, exogenous PMA suppressed the transcription of P. aeruginosa QS genes (lasR, rhlR, and rhlI), and the production of QS signals (3OC12-HSL, C4-HSL) and virulence (pyocyanin). Furthermore, exogenous PMA reduced the infection-related injury in human bronchial epithelial BEAS-2B cells. Prophylactic administration of PMA in mice suppressed P. aeruginosa QS activation, and relieved infection-induced neutrophilic lung injury.
Conclusion: Our findings suggest PMA can serve as a potential anti-QS agent against bacterial virulence in the challenge of P. aeruginosa lung infection.