New Tool for Mining Bacterial Genome for Novel Drugs
Date: 31.1.2013
Vanderbilt biochemists have discovered that the process bacteria undergo when they become drug resistant can act as a powerful tool for drug discovery.
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.
Scientists started with the well-characterized soil bacterium Nocardiopsis. They exposed the bacterium to two different antibiotics -- streptomycin and rifampicin.
"The first thing that happens is almost all of the bacteria die. Less than one cell in a million survives," said Bachmann.The chemists then cultured the survivors without the antibiotic and used McLean's instrumental methods to profile the drug-like compounds that they produced.
They discovered that the differences were much greater than they expected. The survivors had undergone extensive mutations, not only in the genes that produce secondary metabolites but also in the housekeeping genes that alter the way they make RNA and proteins. As a result, they determined that the resistant strains produced more than 300 compounds that were not expressed by the original organism.
