Uridine shows potential as an antibiotic adjuvant to combat the crisis of Gram negative bacterial drug resistance.

Infections caused by multidrug‑resistant Gram‑negative bacteria represent a major global public‑health challenge. Though aminoglycoside antibiotics deliver potent bactericidal effects, their clinical application is greatly constrained by poor bacterial drug uptake and toxic side effects. A study published in Science Advances confirms that uridine can act as a safe adjuvant to markedly amplify the antibacterial activity of aminoglycosides.

The research uncovers a novel mechanism. Pathogens including Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae take up aminoglycosides via carbohydrate transport systems. Uridine induces the expression of multiple sugar transporters to facilitate antibiotic entry into bacterial cells, and this effect does not rely on altering bacterial proton‑motive force.

In vitro assays show that combining uridine substantially improves the inhibitory activity of aminoglycosides against drug‑resistant strains. In artificial urine, human‑blood systems and a mouse urinary‑tract‑infection model, uridine‑gentamicin combinations effectively eliminate pathogens and delay the emergence of resistant mutants.

Notably, uridine is already clinically used for chemotherapy‑related detoxification and is well‑tolerated in humans. This therapeutic strategy may lower aminoglycoside dosages and reduce ototoxic and nephrotoxic risks, offering new adjuvant options for urinary‑tract infections and bacteremia. Further pharmacokinetic and large‑scale in‑vivo studies are required to advance clinical translation.

FOR DETAIL: https://doi.org/10.1126/sciadv.adw7630

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