Mitigating ROS signalling pathway-mediated defence mechanism: a novel approach to counteract bacterial resistance using natural antioxidant-based antibiotics

Abstract

Antibiotic resistance is a critical global health concern and one of the most serious threats to public health worldwide today. In recent decades, resistant pathogenic bacteria have increased significantly, making infections harder to treat. The intra-bacterial generation of ROS (reactive oxygen species), especially under antibiotic stress, plays a crucial role in modulating gene networks that drive bacterial resistance. The ROS-responsive regulons and cellular machinery activate defence responses that promote resistance. Recent studies emphasize the pivotal role of ROS-mediated signalling in activating alternative pathways that enhance bacterial survival under antibiotic pressure. As central mediators of stress perception and adaptation, ROS accelerate the evolution of resistance. Amid growing toxicity and reduced efficacy of current antibiotics, natural dual-active compounds such as berberine, caffeic acid, cannabidiol, curcumin, eugenol, luteolin, menadione, quercetin, and ursolic acid offer promising solutions to overcome the limitations of conventional antibiotics. These compounds possess both antibacterial and antioxidant properties, and can scavenge ROS while simultaneously inhibiting bacterial growth, providing a novel therapeutic approach that effectively bypasses ROS-mediated defence mechanisms in pathogens and enhances antimicrobial potential. The objective of this review is to explore recent advances in ROS-mediated signalling pathways that contribute to antibiotic resistance and to propose a novel strategy for overcoming this challenge by targeting ROS-driven defence mechanisms with natural antioxidant-based antibacterials. Recent literature has highlighted several promising examples of dual-active antibacterial–antioxidant molecules, offering potential breakthroughs in addressing antibiotic resistance. The dual capacity of these compounds to target pathogens and reduce oxidative stress positions them as promising foundations for next-generation antimicrobial therapies.

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