Mycobacterium tuberculosisWikimedia, NIAIDDrugs that interfere with the synthesis of the essential nutrient folate are among the oldest antibiotics around. Now, after decades of successful use, researchers are using metabolomics to discover how, exactly, they work.
One such drug, commonly used to treat tuberculosis (TB), is processed by a key enzyme in folate biosynthesis, breaking down into different products that interfere with enzymes that act later in the pathway. The results, published today (November 1) in Science, contradict the previous belief that the drug, para-aminosalicylic acid (PAS), worked by simply binding the enzyme such that it was not available to process a folate precursor, and may point to novel TB drug targets and antimicrobial strategies beyond enzyme inhibition.
“It’s a really good example of how we don’t really understand how many drugs work,” said Eric Rubin, a tuberculosis researcher at Harvard University who did not participate in the research. “We often operate under the simple assumption that drugs inhibit a process—but ...
