Quorum-Sensing Inhibition as a Novel Strategy for Controlling Bacterial Biofilms
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Background: Bacterial biofilms contribute to persistent and difficult-to-treat infections by protecting microorganisms from antimicrobial agents and host defenses. Quorum sensing (QS) regulates multiple biofilm- and virulence-associated behaviors and has therefore emerged as a potential anti-virulence target. Despite extensive experimental investigation, the translational relevance of QS inhibition remains uncertain because activity varies across organisms, signaling pathways, compounds, and experimental models. Objective: To critically review, using a targeted narrative approach, the biological basis, experimental evidence, therapeutic potential, and translational limitations of quorum-sensing inhibition for controlling bacterial biofilms, with primary emphasis on developments reported between 2019 and 2024. Methods: Published evidence concerning natural and synthetic QS inhibitors, quorum-quenching enzymes and bacteria, antibiotic-QSI combinations, resistance mechanisms, delivery strategies, and clinically relevant biofilm-forming pathogens was narratively synthesized. Experimental evidence addressing biofilm formation, QS-regulated virulence, signaling pathways, gene expression, and antimicrobial susceptibility was prioritized, with particular attention to Pseudomonas aeruginosa and Staphylococcus aureus. Evidence was interpreted according to experimental context and translational relevance; no meta-analysis was performed. Results: Natural products, synthetic QS modulators, and enzymatic quorum-quenching strategies consistently altered one or more QS-regulated phenotypes in experimental systems. Three-hydroxybenzoic acid produced approximately 90% inhibition of S. aureus biofilm activity at 25 µg/mL, while SsoPox-W263I produced greater than 70% biofilm reduction in 6 of 10 evaluated P. aeruginosa clinical isolates. Quorum-quenching bacterial isolates produced approximately 50–60% biofilm reductions in selected multidrug-resistant P. aeruginosa isolates. Antibiotic-QSI combinations showed enhanced antimicrobial activity in experimental models, although human efficacy evidence remained limited. Conclusion: QS inhibition is a promising adjunctive antibiofilm and anti-virulence strategy, but clinical translation requires standardized models, pharmacokinetic and toxicological validation, testing in diverse clinical isolates and mature biofilms, and appropriately designed clinical studies
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1. Kalia VC, Patel SKS, Kang YC, Lee JK. Quorum sensing inhibitors as antipathogens: biotechnological applications. Biotechnol Adv. 2019;37:68–90.
2. Zhou L, Zhang Y, Ge Y, Zhu X, Pan J. Regulatory mechanisms and promising applications of quorum sensing-inhibiting agents in control of bacterial biofilm formation. Front Microbiol. 2020;11:589640. doi:10.3389/fmicb.2020.589640.
3. Sikdar R, Elias M. Quorum quenching enzymes and their effects on virulence, biofilm and microbiomes: a review of recent advances. Expert Rev Anti Infect Ther. 2020;18(12):1221–1233. doi:10.1080/14787210.2020.1794815.
4. Rémy B, Plener L, Decloquement P, Armstrong N, Elias M, Daudé D, Chabrière E. Lactonase specificity is key to quorum quenching in Pseudomonas aeruginosa. 2020.
5. Patel R, et al. A clash of quorum sensing vs quorum sensing inhibitors: an overview and risk of resistance. Arch Microbiol. 2023.
6. Plant-derived natural products against Pseudomonas aeruginosa and Staphylococcus aureus: antibiofilm activity and molecular mechanisms. Molecules. 2020;25(21):5024. doi:10.3390/molecules25215024.
7. Bhattacharya SP, et al. Quorum sensing inhibition and antibiofilm action of triterpenoids: an updated insight. Fitoterapia. 2023.
8. Wang J, Lu X, Wang C, Yue Y, Wei B, Zhang H, Wang H, Chen J. Research progress on the combination of quorum-sensing inhibitors and antibiotics against bacterial resistance. Molecules. 2024;29(7):1674. doi:10.3390/molecules29071674.
9. D'Aquila P, De Rose E, Sena G, Scorza A, Cretella B, Passarino G, Bellizzi D. Quorum quenching approaches against bacterial-biofilm-induced antibiotic resistance. Antibiotics (Basel). 2024;13(7):619. doi:10.3390/antibiotics13070619.
10. Ganesh PS, Veena K, Senthil R, et al. Biofilm-associated Agr and Sar quorum sensing systems of Staphylococcus aureus are inhibited by 3-hydroxybenzoic acid derived from Illicium verum. ACS Omega. 2022;7(17):14653–14665. doi:10.1021/acsomega.1c07178.
11. Targeting acyl homoserine lactones by quorum-quenching bacterial strains to control biofilm formation in Pseudomonas aeruginosa. 2021.
12. Vashistha A, Sharma N, Nanaji Y, Kumar D, Singh G, Barnwal RP, Yadav AK. Quorum sensing inhibitors as therapeutics: bacterial biofilm inhibition. Bioorg Chem. 2023;136:106551. doi:10.1016/j.bioorg.2023.106551.