Bacterial Adaptation to Phytochemical-Induced Redox Stress: Implications for Antibacterial Efficacy and Antibiotic Susceptibility

Plant-derived phytochemicals are being investigated as antibacterial agents and antibiotic adjuvants, but disruption of bacterial redox homeostasis does not invariably lead to sustained killing. This critical narrative review examines how bacterial responses to phytochemical-induced oxidative and electrophilic stress influence antibacterial efficacy and subsequent antibiotic susceptibility. We integrate phytochemical-specific evidence with broader bacterial redox physiology, distinguishing demonstrated mechanisms from molecular associations and mechanistic extrapolations. The synthesis covers thiol modification, metal dyshomeostasis, membrane and respiratory dysfunction, redox-sensitive regulation, antioxidant defenses, repair, and metabolic remodeling. These responses, triggered by phytochemical exposure, can contribute to bacterial protection and recovery, although causal redox involvement remains unresolved in many studies. Depending on the phytocompound, bacterial species, and exposure conditions, observed outcomes include cross-protection, tolerance, persistence, viable-but-nonculturable survival, and antibiotic-specific susceptibility trade-offs. Repeated exposure may additionally select heritable changes that must be differentiated from reversible physiological adaptation. Irreversible redox collapse is interpreted operationally as sustained loss of viability and failure to recover after stress removal. The term denotes an interpretative framework rather than a distinct death mechanism; a redox-dependent contribution requires functional evidence, and recovery failure is assessed within specified assay conditions. ROS fluorescence, ATP depletion, or growth inhibition alone cannot establish this endpoint or its redox dependence. Integrating validated redox measurements and functional interventions with killing and recovery assays, chemical characterization, exposure standardization, and host tolerability can strengthen the evaluation of plant-derived antibacterial compounds and their combinations with antibiotics.