Quorum Sensing and Quorum Quenching in Pseudomonas aeruginosa and Staphylococcus aureus Infections: Therapeutic Potential, Limitations and Clinical Challenges.

Antimicrobial resistance (AMR) represents a major global health threat, largely driven by antibiotic overuse and the protective role of bacterial biofilms. Quorum sensing (QS), a bacterial communication system regulating virulence and biofilm formation, has emerged as a promising therapeutic target. Quorum quenching (QQ), which disrupts QS without directly inhibiting bacterial growth, is considered a potential anti-virulence strategy that may reduce selective pressure for resistance. This review critically evaluates recent advances in QQ research, focusing on its clinical applicability, limitations, and risks. We analyzed studies from the last five years involving natural compounds, synthetic molecules, nanoparticles (NPs), and combination therapies targeting key pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus in models of lung diseases, mainly cystic fibrosis, chronic wounds, burns, and implant-associated infections. While numerous compounds demonstrate significant in vitro anti-biofilm and anti-virulence activity, major challenges remain, including limited in vivo validation, pharmacokinetic constraints, toxicity concerns, microbiome disruption, and the potential development of tolerance or functional resistance. Although QQ offers a promising adjunctive approach to conventional antibiotics, its long-term clinical feasibility requires comprehensive evaluation of evolutionary dynamics, host-microbe interactions, and safety profiles.