Quorum Quenching and Quorum-Sensing Interference in Pseudomonas aeruginosa: Molecular Mechanisms, Host Protection, and Translational Barriers

Quorum sensing (QS) coordinates virulence expression, biofilm-associated behavior, and persistence in Pseudomonas aeruginosa, making its signaling network a potential target for adjunctive anti-virulence therapy. Quorum quenching (QQ) directly degrades, modifies, or sequesters signaling molecules, whereas broader QS interference encompasses inhibition of signal synthesis, receptor antagonism, and disruption of downstream regulatory interactions. Experimental studies of N-acyl-homoserine lactone (AHL)-degrading enzymes and PqsR antagonists have demonstrated suppression of selected virulence-associated phenotypes, with several infection models showing reductions in host injury or persistence-associated outcomes. The PqsE–RhlR regulatory interface has gained substantial molecular and genetic support as a distinct intervention target, but its pharmacological development remains limited. Responses to QS interference vary with bacterial strain, regulatory network adaptation, environmental conditions, and infection stage. Reductions in virulence-factor production or biofilm biomass do not consistently correspond to bacterial clearance or host protection. Available human studies involving agents with proposed QS-modulatory activity have not established clinical benefits specifically attributable to QS inhibition. Clinical translation requires validated target engagement, efficacy assessment in established and polymicrobial infections, and characterization of delivery, pharmacological exposure, safety, and resistance evolution.