Targeting quorum sensing to combat bacterial biofilms: Natural biomass as emerging anti-virulence strategies

Bacterial biofilms are no longer viewed as passive surface-associated aggregates but as highly coordinated, multicellular microbial systems governed by intricate regulatory and metabolic networks. Encased within a dynamically structured extracellular polymeric substance (EPS) matrix, these communities exhibit emergent properties-enhanced tolerance, phenotypic heterogeneity, and adaptive resilience-that challenge conventional antimicrobial paradigms. At the core of this collective behavior lies quorum sensing (QS), a sophisticated communication circuitry that synchronizes gene expression, virulence deployment, metabolic cooperation, and biofilm maturation. The accelerating crisis of antimicrobial resistance necessitates a decisive conceptual shift from bactericidal strategies toward precision interference with microbial social behavior. In this emerging framework, biomass-derived bioactives and nano-enabled natural compounds from plants, endophytes, algae, and their metabolomes are being repositioned as ecological modulators rather than traditional antibiotics. These agents function as quorum quenchers, signal disruptors, and matrix destabilizers, capable of rewiring QS regulatory networks, enzymatically degrading autoinducers, modulating EPS biosynthetic pathways, and attenuating adhesion and virulence expression. By targeting communication hierarchies and cooperative resilience mechanisms, biomass-based interventions dismantle biofilm integrity while minimizing selective evolutionary pressure. This review advances a systems-level perspective on biofilm control, framing natural biomass as a multifunctional, sustainable, and evolution-informed platform for anti-virulence therapy. By integrating insights from microbial ecology, nanobiotechnology, and chemical signaling interference, we highlight a transformative shift toward next-generation strategies that disrupt bacterial collective intelligence rather than merely suppress growth.