Exterminating resistance via an enzyme
Discovery could boost TB drugs
A molecular biologist and Nobel laureate at Yale University has found a way to rob bacteria of their ability to resist drugs. Eventually, the technique could be used to restore sensitivity to all first-line agents against tuberculosis.
Sidney Altman, PhD, professor of biology at Yale, has developed a way of destroying the mechanism by which bacteria protect themselves against drugs by targeting the resistance mechanism in the bacteria.
So far, Altman has used the technology to block the genetic activity that makes bacteria resistant to two antibiotics: chloramphenicol and ampicillin. But the same method will work equally well for all bacteria, including Mycobacterium tuberculosis, Altman says assuming the mechanism that creates resistance is known. For some drugs used to fight TB, but not all, that knowledge already exists.
Altman’s method takes advantage of the capabilities of an enzyme he has spent decades studying.
"We place a small piece of RNA inside a cell that’s custom-designed to make a complex with the target-messenger RNA responsible for the drug resistance," he says. "That little complex is recognized by an enzyme in the cell, and it destroys the target RNA."
Altman’s findings grew out of basic research he has been doing for the past 25 years on the enzyme that destroys the complex. In 1989 he was awarded the Nobel Prize for his work on RNA. He found that RNA is not just a passive carrier of a genetic code but also can function as an enzyme that engages in chemical reactions. Only in the past seven years has he tried using the enzyme to destroy the mechanism for drug resistance, he adds.
The next step in his work will be to test the method on animals, says Altman.
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