A new class of antibiotic that one day could fight drug-resistant bacteria has been discovered, according to a study in the Oct. 24 issue of the journal Science.
Researchers found a new class of synthetic antibacterial chemicals—called the CBR703 series—that inhibits RNA polymerase, the key enzyme in gene expression. Knowing exactly how these chemicals keep bacterial cells in check can help scientists create antibiotics that are more effective.
According to the study, the CBR703 series chemicals hindered the ability of RNA polymerase in Escherichia coli to perform crucial functions, such as building molecules of RNA. They rendered RNA polymerase useless by binding to a specific place on the enzyme, which is a necessary step in the process.
Researchers chose to study the effects of CBR703 inhibitors on E. coli, since the RNA polymerase enzyme in many pathogens is similar to that found in the E. coli bacteria. While the CBR703 inhibitors stopped gene expression in E. coli, researchers found that the compounds would not inhibit RNA polymerase in human cells. Finding the reason for this lack of inhibition in human cells is important in designing new drugs, as some antibiotic compounds could harm both bacteria and human cells.
"When we find something that inhibits a particular process, it’s easier to make targeted drugs," said Irina Artsimovitch, Ph.D., study coauthor and an assistant professor of microbiology at The Ohio State University, Columbus. "In this case, finding something that inhibited bacterial RNA polymerase lets us look at the structure of the enzyme and determine how to improve the inhibitors further to make them more effective.
"Knowing how a new antibiotic acts on its target takes the process of making new drugs to a new level, allowing for better understanding of a drug’s direct and side effects," she said. "This new series of antibacterial compounds holds great promise for designing drugs specifically targeted to major classes of bacterial pathogens, such as those that cause pneumonia and tuberculosis."
