Researchers have discovered a way to make bacteria more vulnerable to a class of antibiotics known as quinolones, according to a paper published last week in the journal Molecular Cell.
Quinolones target bacterial enzymes called topoisomerases which help DNA replicate and repair. While they are a commonly used treatment against bacteria such as Escherichia coli and Staphylococcus aureus, they often fail against infections with a high density of bacteria.
The study was led by a former MIT postdoc and a recent Boston University PhD recipient. The duo drew from a 2011 study, which found that delivering a type of sugar along with aminoglycoside antibiotics helps boost bacterial metabolism, making it more likely that the bacteria will undergo cell death in response to the damage caused by the antibiotic.
For the current study in quinolones, the researchers had to add a terminal electron acceptor along with the sugar. Electron acceptors play an important role in cellular respiration. While oxygen is generally the electron acceptor in cells, for the purposes of the study, fumarate was used instead.
The fumarate, glucose and quinolone combination was able to eliminate several types of bacteria in high-density bacterial colonies more effectively than the antibiotic alone.
"This finding highlights that the metabolic state of the bug significantly influences how the antibiotic will impact the bug. And, for the antibiotic to be effective as a killing agent, it requires downstream cellular respiration as part of the process," said James Collins, the Termeer Professor of Medical Engineering and Science in MIT's Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering and the senior author of the study.
In the future, the scientists hope to test this approach in animal models of bacterial infection and also to find other antibiotics that can be modified in this way.