Decoding the silent conversations: targeting quorum sensing to disarm bacterial pathogens in the age of antimicrobial...

Antimicrobial resistance (AMR) has emerged as a global health challenge, imposing significant clinical and economic burdens worldwide. The widespread and often indiscriminate use of antibiotics has accelerated resistance, necessitating alternative therapeutic strategies to combat microbial pathogenicity. Quorum sensing, a cell density-dependent signalling system, represents a promising target in this aspect. This review examines the molecular framework of quorum sensing across diverse microbial communities, its signalling cascades, and its role in regulating biofilm formation, efflux pump modulation and horizontal gene transfer with the quorum signalling. It further discusses quorum-sensing inhibition strategies, including natural products, synthetic compounds, quorum-quenching enzymes, and antibody-mediated and vaccine-mediated approaches. Application of CRISPR/Cas, engineered probiotic strains and nanocarrier-mediated delivery systems for quorum signalling disruption has been addressed. A key strength of this review is that it is the first to combine the underlying molecular mechanisms of quorum sensing with future translational tools such as artificial intelligence, CRISPR, engineered probiotics and nanotechnology to develop next-generation anti-virulence solutions for drug-resistant infection. While the preclinical findings have several challenges specific to the specificity and pharmacokinetic properties, strategies to resolve these considerations have been discussed. Overall, quorum signalling as a target is a major paradigm shift that may offer sustainable antimicrobial therapy to fight the global antimicrobial resistance issue. This can be achieved through a multidisciplinary approach to optimise antimicrobial therapy beyond the traditional concept of "killing".