Phenolic-rich blueberry extract enhances gentamicin efficacy against multidrug-resistant Acinetobacter baumannii BAA1605 via efflux inhibition and suppression of antibiotic-induced metabolic activation

The growing threat of antibiotic resistance calls for novel strategies to enhance antimicrobial efficacy. Blueberries, rich in phenolic compounds, have attracted attention as food-derived agents capable of modulating bacterial resistance mechanisms. This study explores the potential of phenolic-rich blueberry extracts as antibiotic resistance-modifying agents. To evaluate their modulatory effects, we conducted antibacterial testing, efflux pump inhibition assays, and transcriptomic analyses on Acinetobacter baumannii BAA-1605 treated with blueberry extract, gentamicin, and their combination. While the extract alone showed no direct antibacterial activity, its combination with gentamicin resulted in a twofold reduction in lowering the minimum inhibitory concentration against Acinetobacter baumannii BAA-1605. Mechanistic assays revealed that blueberry extract enhanced gentamicin’s effect on inhibiting efflux pump activity. Transcriptomic analysis showed that the combination treatment of blueberry extract and gentamicin modulated genes involved in metabolism, stress response, and virulence, with Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment pointing to altered energy production and cellular adaptation pathways. These findings suggest that blueberry phenolics do not act bactericidally but may affect bacterial physiology to potentiate gentamicin action. This study highlights the potential of natural plant phenolic compounds as antibiotic adjuvant and supports further investigation in their fighting against multidrug-resistant pathogens.