QUORUM SENSING-MEDIATED VIRULENCE REGULATION IN PSEUDOMONAS AERUGINOSA: CURRENT ADVANCES AND THERAPEUTIC IMPLICATIONS

Abstract

Pseudomonas aeruginosa is a major opportunistic pathogen responsible for a wide range of healthcare-associated infections and is recognized as one of the leading causes of multidrug-resistant (MDR) bacterial infections worldwide. Its remarkable ability to establish persistent infections is largely attributed to quorum sensing (QS), a sophisticated cell-to-cell communication system that coordinates the expression of numerous virulence determinants, including biofilm formation, motility, exotoxin production, pyocyanin synthesis, elastase secretion, and antimicrobial tolerance. The QS regulatory network of P. aeruginosa comprises four interconnected signaling systems—Las, Rhl, Pseudomonas quinolone signal (PQS), and integrated quorum sensing (IQS)—which collectively regulate bacterial adaptation, pathogenicity, and persistence within the host. This narrative review summarizes the molecular mechanisms underlying QS-mediated virulence regulation in P. aeruginosa and discusses its pivotal role in biofilm development, chronic infection, and antimicrobial resistance. Recent advances in quorum-quenching strategies, including enzymatic degradation of signaling molecules, natural and synthetic quorum-sensing inhibitors, nanotechnology-based drug delivery systems, bacteriophage-mediated approaches, and combination therapies with conventional antibiotics, are critically evaluated. Furthermore, the challenges associated with the clinical translation of QS-targeted therapies, including pathway redundancy, emergence of QS-deficient mutants, and pharmacological limitations, are discussed along with future research directions. Targeting bacterial communication rather than bacterial viability represents a promising anti-virulence strategy that may reduce selective pressure for antimicrobial resistance while enhancing the efficacy of existing antibiotics. Continued advances in molecular microbiology, medicinal chemistry, and translational research are expected to facilitate the development of clinically effective quorum-sensing-based therapeutics for the management of MDR P. aeruginosa infections.