An antibiotic used for decades could regain some of its effectiveness against certain resistant bacteria. Researchers have associated vancomycin with a small molecule called pghi-4. This combination restored the drug's action against resistant enterococci, in the laboratory and in mice.
Vancomycin is used against serious infections caused by certain bacteria. Its use has become more difficult with the emergence of Enterococcus faecium bacteria resistant to this antibiotic. These can cause hard-to-treat hospital infections.
Bacteria - Unsplash illustration
The team targeted a bacterial enzyme called SagA. It participates in the repair and remodeling of the wall that protects the bacterium. This envelope also constitutes the target of vancomycin, which normally prevents it from maintaining itself.
The molecule pghi-4 blocks the activity of SagA. This inhibition disrupts the construction of the wall of Enterococcus faecium. Vancomycin can then better reach its target and prevent the bacterium from maintaining a functional envelope.
In the laboratory, the combination restored vancomycin's ability to kill several resistant strains. The amount of antibiotic needed decreased up to eightfold in some tests. The researchers also observed a reduction in bacterial load in a mouse model of sepsis.
The result does not yet turn pghi-4 into an available treatment. The experiments were conducted on cells, clinical isolates, and mice. The efficacy and safety of this combination still need to be evaluated in humans.
The approach belongs to the family of antibiotic adjuvants. These auxiliary molecules do not necessarily fight bacteria alone. Instead, they neutralize a resistance mechanism to prolong the usefulness of an existing antibiotic.
This strategy could reduce the time needed to develop a treatment, since the main molecule is already known. However, the results remain preclinical. Additional studies will need to verify the pharmacology, toxicity, and ability of the combination to work in patients.