( adimir Svetlov a study co-author and a...)Researchers find how some antibiotics kill bacteria

"Those mutations could render these antibiotics ineffective against most of the serious health threats that they are being used to manage," he continued.

All rifamycins belong to one of two structural classes. The researchers used two clinically important rifamycins ?rifapentin and rifabutin ?that represent each structural class. They obtained samples of the antibiotics in their respective crystal structure form. Crystal structures are sets of atoms arranged in ways that are unique to a particular substance.

The researchers used a technique called X-ray crystallography to determine where individual atoms are located within a crystal structure. From this information they then created high-resolution computer models of each antibiotic, approximating what each substance looked like on the atomic level and exactly how each bound to and affected a key component of bacteria called RNA polymerase.

RNA polymerase is the machinery that keeps bacteria going ?a bacterium cannot carry out gene expression without it. Cut off gene expression and bacteria are dead. In their study, the researchers looked at the effects of rifapentin and rifabutin on E. coli RNA polymerase.

With recent advances in X-ray crystallographic studies of RNA polymerase, the researchers could determine exactly where and how both antibiotics bound to RNA polymerase in E. coli, and what it did to that polymerase as a result.

The results provide new evidence of how rifamycins inhibit pathogenic bacteria. That finding applies to all rifamycins, Artsimovitch said.

The study showed that rifamyacins inhibit pathogenic bacteria by removing the crucial magnesium ion (Mg2+) from a bacterium's RNA polymerase.

"Removing this ion is like removing spark plugs from an engine," Artsimovitch said. "The car may look fine, but it won't run.

"Until we could look under
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Source:Ohio State University