Bacterial SOS response inhibition with green tea epicatechin impairs ciprofloxacin-driven resistance evolution in Escherichia coli

Bacterial stress responses play a central role in accelerating the emergence of antibiotic resistance. Fluoroquinolones like ciprofloxacin trigger the SOS response, a conserved pathway that promotes DNA repair while increasing genetic variability, facilitating bacterial adaptation to antibiotic pressure. Targeting the SOS response therefore represents a promising strategy to potentiate antibiotic activity and control resistance evolution. This study investigates epicatechin, a plant-derived antioxidant, as a potential inhibitor of SOS activation during ciprofloxacin exposure in Escherichia coli . We show that epicatechin attenuates the induction of the SOS master regulator RecA and other effectors like SulA in a dose-dependent manner at both population and single-cell levels. This effect was consistent across laboratory and clinical strains with distinct susceptibility profiles. Beyond SOS inhibition, quantitative proteomic analysis revealed that epicatechin broadly downregulates major DNA repair pathways together with oxidative stress and general stress responses. While preserving ciprofloxacin antimicrobial activity, epicatechin modulated downstream adaptive processes, reducing plasmid conjugation efficiency and constraining long-term ciprofloxacin resistance evolution by limiting mutagenesis. Together, these findings identify epicatechin as a potent modulator of bacterial stress adaptation. Our results support its potential as a chemical scaffold for the development of SOS-targeting adjuvants to limit the emergence and spread of antimicrobial resistance.