Lan-Tu Xiong, Ming-Ming Guan, Wan-Yu Gong, Wan-Jun Li, Di Zhu, Ya-Sheng Li, Alastair N Herron, Yu Shi, Quan Zeng, Ze-Ling Xu, Xin Deng, Zi-Ning Cui
Quorum sensing (QS), a sophisticated cell-cell communication system in microorganisms, governs collective behaviors such as virulence, biofilm formation, and antibiotic resistance in a population-density-dependent manner. Targeting QS with quorum sensing inhibitors (QSIs) has emerged as a promising anti-virulence strategy to combat bacterial pathogens without exerting lethal selective pressure, thereby potentially curbing the rise of antimicrobial resistance. This review provides an integrated overview of the molecular mechanisms of QS signaling networks in Gram-negative and Gram-positive bacteria, and extends the discussion to cross-kingdom communication and QS-like systems in fungi and bacteriophages. We systematically categorize QSIs based on their origins (plant, microbial, animal, and synthetic) and detail their mechanisms of action, focusing on the interference with autoinducer synthesis, degradation, receptor binding, and downstream signal transduction. Beyond a mere compilation of research advances, we critically evaluate the translational potential of QS interference, highlighting recent applications in clinical medicine (e.g., anti-biofilm coatings), agriculture (biocontrol agents), and environmental engineering (biofouling mitigation). Finally, we identify key challenges such as in vivo efficacy, ecological impact, and the translational gap, and propose future research priorities centered on smart delivery systems, narrow-spectrum inhibitors, and interdisciplinary collaboration. This comprehensive analysis underscores QS interference as a versatile and sustainable strategy, while charting a course for its evolution from a laboratory phenomenon to a practical solution.