Membrane-enclosed quinolone signal attenuates bacterial virulence by interfering with quorum sensing.

Outer membrane vesicle (OMV)-delivered quinolone signal (PQS) plays a critical role in cell-cell communication in . However, the functions and mechanisms of membrane-enclosed PQS in interspecies communication in microbial communities are not clear. Here, we demonstrate that PQS delivered by both OMVs from and liposome reduces the competitiveness of , which usually shares the same niche in the lungs of cystic fibrosis patients, by interfering with quorum sensing (QS) in through the LysR-type regulator ShvR. Intriguingly, we found that ShvR regulates the production of the QS signals cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) by directly binding to the promoters of signal synthase-encoding genes. Perception of PQS influences the regulatory activity of ShvR and thus ultimately reduces QS signal production and virulence in . Our findings provide insights into the interspecies communication mediated by the membrane-enclosed QS signal among bacterial species residing in the same microbial community.IMPORTANCEQuorum sensing (QS) is a ubiquitous cell-to-cell communication mechanism. Previous studies showed that mainly employs cis-2-dodecenoic acid (BDSF) and N-acyl homoserine lactone (AHL) QS systems to regulate biological functions and virulence. Here, we demonstrate that quinolone signal (PQS) delivered by outer membrane vesicles from or liposome attenuates virulence by targeting the LysR-type regulator ShvR, which regulates the production of the QS signals BDSF and AHL in a. Our results not only suggest the important roles of membrane-enclosed PQS in interspecies and interkingdom communications but also provide a new perspective on the use of functional nanocarriers loaded with QS inhibitors for treating pathogen infections.