Scientists have discovered a novel method that certain strains of bacteria use to counter the effects of certain antibiotics. The finding, published online in Science, could help drug researchers create new compounds that work in conjunction with established antibiotics to overcome a bacterium’s resistance mechanism.
The discovery comes at an opportune time as Congress considers legislation that would boost antibiotic-resistance research and provide incentives for companies to develop new therapies targeting drug-resistant bacteria.
On a molecular level, some antibiotics work by binding to and inhibiting the bacteria’s ribosomes, which are essential for synthesizing proteins that are vital to cells’ survival. Scientists have been puzzled by how some bacteria evolve in ways that prevents this binding, thus making a formerly potent antibiotic ineffective. Researchers from the Pennsylvania State University in University Park and Northwestern University in Evanston, Ill, report a clue that they say could lead to solving the puzzle.
Using x-ray crystallography, researchers created a 3-dimensional picture of what happens on a molecular level that allows a bacteria strain to resist an antibiotic’s effects. They focused on the activity of an enzyme, RlmN, that facilitates the proper function of the ribosome by attaching a small molecular tag to one of its components. Several years ago, genetic studies showed a bacterium that causes disease in humans, Staphylococcus aureus, acquired a gene from other bacteria, allowing it to produce a novel protein that has the same function as RlmN but places the tags at a different location, which prevents an antibiotic that normally binds with the ribosome from doing so.
Squire Booker, PhD, coauthor and an associate professor at Pennsylvania State, in a release, called the finding exciting because it shows a new chemical mechanism for methylation. “Because we know the specific mechanism by which bacterial cells evade several classes of antibiotics, we can begin to think about how to disrupt the process so that standard antibiotics can do their jobs.”