Abstract
The emerging global threat of antimicrobial resistance (AMR) has necessitated the urgent search for new alternatives to conventional antibiotics. Interfering with quorum sensing (QS) is identified as an attractive next-generation antimicrobial approach. Quorum sensing inhibitors (QSIs) offer an intriguing approach by reducing pathogenicity without affecting bacterial growth or viability, thereby lowering selective pressure for resistance development. Natural products, particularly mushroom-derived ones, represent an immense and untapped reservoir of such anti-virulence compounds. In this review, the potential of mushrooms as a source of novel QSIs is discussed, as reflected in their diverse bioactive compounds, multidirectional mechanisms of action, species-specific activity, and synergistic interaction with conventional antibiotics. We describe the anti-quorum sensing and antimicrobial activities shown in a wide range of mushroom species, from commonly farmed species to wild medicinal mushrooms, and emphasize the high value of this comparatively unexplored source. We also critically evaluate current research limitations, high-throughput screening approaches, and major future priorities for the clinical use of QSIs from mushrooms against resistant infections.