Pseudomonas aeruginosa is an opportunistic pathogen responsible for severe and persistent infections, especially in immunocompromised patients. Its high adaptability and antibiotic resistance are largely mediated by quorum sensing (QS), a cell-to-cell communication system that coordinates the expression of virulence factors and biofilm formation. Targeting QS-rather than bacterial viability-has emerged as a promising antivirulence strategy known as quorum quenching (QQ). This review analyses current QQ approaches against P. aeruginosa, emphasizing their mechanisms, efficacy, and translational potential. Five main strategies are discussed: (i) inhibition of autoinducer synthesis through enzyme blockers targeting LasI, RhlI, and Pqs biosynthetic enzymes; (ii) enzymatic degradation or inactivation of QS signals by lactonases, acylases, and oxidoreductases; (iii) interference with signal release, particularly via disruption of outer membrane vesicle formation; (iv) inhibition of QS receptors (LasR, RhlR, and PqsR) using natural and synthetic antagonists; and (v) suppression of downstream signalling cascades. Although significant advances have been achieved, the clinical translation of QS inhibitors remains limited by issues of molecular stability, strain variability, and bioavailability. Nevertheless, structure-guided inhibitor design, synergistic combinations with antibiotics, and biofilm-targeted delivery systems are expanding the therapeutic landscape. Overall, QQ represents a sustainable strategy to attenuate bacterial virulence while minimizing selective pressure for resistance, offering a paradigm shift in the treatment of P. aeruginosa infections and other multidrug-resistant pathogens.
Sánchez-Mateos et al. (Wed,) studied this question.