By pitting various strains of bacteria against one another, researchers from Vanderbilt University have stumbled upon a novel way of discovering active chemicals that can be used to produce powerful new drugs.
Above: Sample dish with a series of co-cultures of competing microorganisms.
Scientists aren’t sure how many species of bacteria there are on Earth (estimates vary—often by several orders of magnitude), but everyone agrees there are a lot. Each strain has its own unique set of biologically active chemicals, many of which are held in reserve for future use. These compounds, called secondary metabolites, protect bacteria and are often used to attack intruders. But these natural chemicals can also be used as ingredients in medicines, including compounds found in antibiotics and anticancer drugs.
Individual bacteria can carry hundreds of these secondary metabolites, but biologists have struggled to coax microbes into producing these chemicals on their own. Synthesizing them has also proven difficult. To get around these challenges, a research team headed by Associate Professor of Chemistry Brian Bachmann and Stevenson Professor of Chemistry John McLean pitted various strains of bacteria against each other, in what the research team dubbed “fight clubs” in a recent press release.
By doing so, different species of bacteria were compelled to compete with one another — a confrontation that revealed their unique versions of biochemical warfare. What’s more, interactions between organisms produced a “co-culture” of compounds that were likewise unique. The results of this work now appears at ACS Chemical Biology.
As a proof of concept, the researchers challenged the soil bacteria Nocardiopsis to one-on-one duels against four different microbial challengers, including a common gut organism, a bacteria that infects people with compromised immune systems, and a microorganism that degrades hydrocarbons. This process allowed the researchers to discover more kinds of biological molecules than the two monocultures combined — co-cultures that contained somewhere between 20,000 to 50,000 different kinds of molecules. A new method called SOM, or self-organizing metabolics map, allowed the researchers to sort all these chemicals in a meaningful way.
Image: a graphic representation of the process the scientists used to discover the new antibiotic, circomicin, with anti-cancer activity. (Bachmann Lab, Vanderbilt University)
The confrontation between Nocardiopsis and Rhodococcus wratislaviensis was particularly fruitful, an exchange the allowed the researchers to discover an entirely new class of dynamic biomolecules. The new compound was named ciromicin, meaning war/cite/disturb/invoke. This new compound has anti-tumor capabilities and the ability to modulate genes involved in programmed cell death.
The study shows that unique metabolic responses under “fight club” conditions can be harnessed to both discover and create previously unidentified bio-chemicals, many of which can be leveraged in medicine.
Read the entire study at ACS Chemical Biology: “Mapping Microbial Response Metabolomes for Induced Natural Product Discovery”.