Antibiotic Resistant Bacteria Are a Source for Novel New Drugs

Drug developers seeking new bacterially synthesized drugs have recognized that bacterial genomes contain a large number of "silent genes" that code for drug-like compounds, known as secondary metabolites. However, it is has proven to be very difficult to turn on the production of these compounds.

Investigators at Vanderbilt University (Nashville, TN, USA) used advanced metabolomic analysis techniques such as ultra-performance liquid chromatography–ion mobility–mass spectrometry to characterize compounds produced by a cohort of streptomycin- and rifampicin-resistant mutants of Nocardiopsis, a soil-derived actinomycete, grown in the absence of antibiotics.

They reported in the January 22, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that the resistant strains produced more than 300 compounds that were not expressed by the original organism. Five of these compounds were both unique enough and abundant enough to be isolated and their molecular structures determined and tested for biological activity.

"Normally, we only find one compound per organism, so this is a significant improvement in yield, allowing us to get many new compounds from previously mined microorganisms," said senior author Dr. Brian Bachmann, associate professor of chemistry at Vanderbilt University. "What we are looking for are new species of molecules in the mutants that are the most unique and the most abundant."

"It is 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 Dr. Bachmann. "This technique is something like fracking in the natural gas industry. We have known for a long time that there were large amounts of underground natural gas that we could not 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."

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