Using bacterial ‘fight clubs’ to find new drugs

Creating bacterial “fight clubs” is an effective way to find new drugs from natural sources. That is the conclusion of a team of Vanderbilt chemists who have been exploring ways to get bacteria to produce biologically active chemicals that they normally hold in reserve. These compounds are called secondary metabolites. They are designed to protect their bacterial host and attack its enemies, so they often have the right kind of activity to serve as the basis for effective new drugs. In fact, many antibiotics and anticancer compounds in clinical use are either secondary metabolites or their derivatives.

In a proof-of-concept test of the fight-club procedure, the research team headed by Associate Professor of Chemistry Brian Bachmann and Stevenson Professor of Chemistry John McLean discovered a promising new class of natural compounds that exhibit anti-cancer activity. The discovery is reported in the article “Mapping microbial response metabolomes for induced natural product discovery” published online by the journal ACS Chemical Biology on June 17.

Bacteria represent a vast untapped reservoir of biologically active compounds. There are an estimated five million trillion trillion bacterial cells on earth. They come in an astounding variety with the best estimate of the number of distinct species ranging from 120,000 to 150,000. Analysis of microbial genomes has shown that individual bacteria carry the blueprints for hundreds of secondary metabolites. However, biologists have had a hard time either getting bacteria to produce them or synthesizing them directly so they can assess their therapeutic value. That’s where the “fight club” approach comes in. Research associate Dagmara Derewacz came up with the idea of applying the analytical tools the Bachmann and McLean groups had developed to analyze what happens when microbes compete. “It’s a ‘shoot first and ask questions later approach,'” said Bachmann, “which is opposite of the traditional approach to natural products drug discovery.” Source: Using bacterial ‘fight clubs’ to find new drugs

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