Exogenous glutamate potentiates gentamicin to kill multidrug- and carbapenem-resistant Pseudomonas aeruginosa through activating biosynthesis of unsaturated fatty acids

Antibiotic-resistant Pseudomonas aeruginosa is a major clinical challenge due to limited drug uptake. This study shows that exogenous glutamate restores gentamicin efficacy by reprogramming bacterial metabolism to enhance membrane permeability. The effect is mediated through increased biosynthesis of unsaturated fatty acids, which is further confirmed by oleic acid supplementation. These findings reveal a novel metabolic approach to overcome multidrug and carbapenem resistance, offering a promising adjunct strategy to improve antibiotic treatment outcomes.