Vanderbilt biochemists have discovered that the process bacteria undergo when they become drug resistant can act as a powerful tool for drug discovery.
Their findings reported this week in the Online Early Edition of the Proceedings of the National Academy of Sciences should give a major boost to natural products drug discovery the process of finding new drugs from compounds isolated from living organisms by substantially increasing the number of novel compounds that scientists can extract from individual microorganisms.
Bacteria have traditionally been the source of important drugs such as antibiotics and anticancer agents. Researchers looking for new bacterially synthesized drugs have long known that bacterial genomes contain a large number of "silent genes" that contain the instructions for making drug-like compounds. But, until now, scientists have found it is very difficult to find ways to turn on the production of these compounds, known as secondary metabolites.
While investigating how bacteria develop drug resistance, Vanderbilt biochemists Brian Bachmann and John McLean discovered that strains of antibiotic-resistant bacteria express hundreds of compounds not produced by their progenitors, many of which are potential secondary metabolites.
"It's as if the bacteria respond to the assault by the antibiotic with a 'save-all-ships' strategy of turning on hundreds of silent genes," said Bachmann, associate professor chemistry at Vanderbilt.
"This technique is something like fracking in the natural gas industry. We've known for a long time that there were large amounts of underground natural gas that we couldn't extract using conventional methods but now we can, using hydraulic fracturing technology. In a similar fashion we think we can use bacteria's antibiotic resistance to intensively mine the bacterial genome for new drug leads," he said.
The original purpose of the study was to take the most det
|Contact: David Salisbury|