Recent research has unveiled a significant breakthrough in the field of antibiotic treatment, highlighting the role of aminoglycosides in combating bacterial infections. Published in Science Advances on September 5, 2025, the study reveals how aminoglycosides can effectively cross the double membrane barrier of Escherichia coli, a common bacterium responsible for various infections. This finding has the potential to transform how we approach antibiotic resistance moving forward.
Aminoglycosides are bactericidal agents that inhibit protein synthesis. They are particularly good at fighting a wide range of pathogens like E. coli, Pseudomonas aeruginosa and Staphylococcus aureus. This insures that they are needed for the treatment of life-threatening diseases such as urinary tract infections, sepsis and endocarditis. The study’s conclusions indicate that pairing aminoglycosides with uridine may have a dramatic synergistic effect that can greatly improve their efficacy.
In follow up work, researchers found that uridine can increase the levels of sugar transporters in E. coli bacteria by a factor of two. It is already widely adopted for non oncology clinical practice purposes. This increase results in a tenfold improvement in the bacteria’s resistance to aminoglycosides. In addition, several strains of drug-resistant and even multidrug-resistant bacteria exhibited increased sensitivity to aminoglycosides when uridine was present.
“Uridine is actually already used in clinical practice for different indications. Its lack of toxicity in humans has already been demonstrated, which will allow us to save time synthesizing new molecules, conduct clinical trials very quickly, and thus reduce the costs of bringing products to market.” – Didier Mazel
The route of entry by which aminoglycosides enter bacterial cells has been discussed for decades. Previously, it was believed that these antibiotics blindly bind to the bacterial cell envelope. Using fluorescent aminoglycosides, the researchers found that these compounds are taken up by E. coli through carbohydrate transport doors.
“Using fluorescent aminoglycosides in particular, we observed that they were entering E. coli bacteria actively through the gateways used by the various carbohydrates. It is the first time that antibiotics have been shown to use this mode of transport.” – Baharoglu
This innovative mechanism offers the potential for aminoglycosides to be employed at lower concentrations or shorter treatment durations in a more targeted fashion. So naturally, we want to broaden their use to other diseases such as endocarditis and septic shock.
“This is a major discovery that could be a game changer for this antibiotic class,” said Baharoglu, emphasizing its potential impact.
This important research highlights the critical need for fundamental scientific research, because it led in unexpected directions that are now key to fighting antibiotic resistance.
“This work also highlights the importance of basic research. Without it, this discovery, which could play a key role in future strategies to combat antibiotic resistance—would not have been possible.” – Didier Mazel
Developments behind the scenes are just around the corner for this combination therapy. Such a development would help radically change how we administer antibiotics, better targeting when we use them and allowing them to be more effective against resistant strains.