French Research Reveals Novel Strategy to Combat Antibiotic Resistance
A groundbreaking study led by the Pasteur Institute, published in Science Advances in September 2025, has unveiled a new understanding of how aminoglycoside antibiotics interact with bacteria – and a potential solution to the growing crisis of antibiotic resistance. The World Health Organization (WHO) has warned that antibiotic resistance poses a public health threat as severe as climate change, potentially leading to around ten million deaths globally by 2050.
Aminoglycosides are crucial in treating infections caused by bacteria responsible for urinary infections, endocarditis, and septicemias, but their effectiveness is increasingly hampered by bacterial resistance. Traditionally, the mechanism of aminoglycoside transport into bacteria was debated, with an older hypothesis suggesting passive diffusion through the bacterial wall. However,the Pasteur Institute’s research demonstrates a different reality.
Researchers initially studied vibrio cholerae (the bacteria causing cholera) and observed a direct correlation between aminoglycoside effectiveness and the presence of sugar transporters – entry points bacteria use to absorb glucose, sucrose, and fructose. This led them to investigate Escherichia coli,revealing that aminoglycosides actively utilize these same sugar entry gates to penetrate the bacterial cell. This is the first confirmed evidence of this active transport mechanism.
Building on this finding, the team successfully increased the number of sugar transporters in E. coli by manipulating the sugar environment. They then screened 200 compounds to identify one that could enhance transporter production and, consequently, antibiotic permeability.
The most promising candidate emerged as uridine, a pyrimidine nucleoside essential for RNA synthesis and involved in glycogen and neuronal membrane production. Tests on human biological samples contaminated with E.coli and in an animal model of urinary infection showed that uridine increased the quantity of sugar transporters in E. coli twofold, and dramatically increased their sensitivity to aminoglycosides tenfold.
Crucially, the research demonstrated that even resistant and multi-resistant bacteria could regain permeability to aminoglycosides in the presence of uridine.This finding opens the door to potentially reducing antibiotic dosages, thereby minimizing the risk of inducing further resistance and reducing toxic side effects – aminoglycosides can be toxic to the kidneys and inner ear at high concentrations.
Future clinical trials will be essential, but the research suggests two promising avenues: administering uridine alongside aminoglycosides to enhance their effectiveness, or “grafting” uridine onto antibiotics to facilitate their entry into resistant bacteria. This French research represents a notable step forward in the fight against antibiotic resistance, offering a novel and potentially transformative approach to tackling this global health challenge.
