Plant phenolic acids enhance antibiotic efficacy against multidrug-resistant extraintestinal pathogenic Escherichia coli

Le résumé fourni par la source

The rise of antibiotic-resistant pathogens presents an unprecedented challenge to global public health. As the discovery of new antibiotics remains time-intensive and costly, extending the utility of existing antibiotics offers a promising alternative. This study aims to investigate the potential of a series of small phenolic acids, natural plant-derived signaling and defense molecules, as potent enhancers of tetracycline activity against multidrug-resistant Escherichia coli (E. coli) strains. Whole-cell biosensor assays, fluorescence probe experiments, transcriptomics, RT−qPCR, molecular docking, gene knockout analyses, resistance evolution experiments, and in vivo infection assays demonstrate that phenolic acids enhance bacterial tetracycline uptake, resulting in synergistic antibacterial effects. Mechanistic investigations reveal that this synergy stems from the disruption of efflux pump activity, proton motive force, and inner membrane permeability, despite a reduction in reactive oxygen species levels. The combinatorial efficacy of phenolic acids and tetracycline was further validated in Galleria mellonella infected with extraintestinal pathogenic E. coli. Moreover, evolutionary experiments show that these combinations slow the emergence of antibiotic resistance compared to tetracycline alone. This study establishes small phenolic acids as promising antibiotic potentiators, expanding the arsenal against multidrug-resistant pathogens.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.