Bacteria produce a medley of secondary metabolites in response to their environment. Often, these metabolites are used to fend off rival microorganisms, making them ideal antibacterial and anticancer drug candidates. However, many of these metabolites are not produced when bacteria are grown in monoculture. A group of Vanderbilt University chemists solved this problem by organizing a microbial fight club.
Brian Bachmann, Associate Professor of Chemistry, and John McLean, Stevenson Professor of Chemistry, describe their unique approach to drug discovery in the journal ACS Chemical Biology (ACS Chem Biol. 2015 Jun 17). The group co-cultured the soil-dwelling bacterium Nocardiopsis with Escherichia coli, Bacillus subtilis, Rhodococcus wratislaviensis, and Tsukamurella pulmonis.
They looked for secondary metabolites in the co-culture media using ion mobility-mass spectrometry, a technique that sorts molecules based on their size to weight ratio. This approach identified upwards of 2,500 unique molecules from each co-culture. In each case, more metabolites were found in the co-culture than in either individual culture combined, suggesting that unique metabolites were produced when different species interacted.
To identify metabolites that were similar in structure to known antibiotics and anticancer drugs, the researchers developed a "self-organizing metabolomics map". This approach identified a unique metabolite from the Nocardiopsis/Rhodococcus co-culture, a macrolactam type polyketide now named "ciromicin".
This isn't the Bachmann Lab's only creative approach to drug discovery. In collaboration with Hazel Barton, Professor of Microbiology and Geology at the University of Akron, Bachmann looked for novel antibiotics made by cave-dwelling bacteria. One sample from Lechuguilla Cave in New Mexico contained 38 antibiotic compounds, an impressive figure when you consider there are fewer than 100 known antibiotics.
Sources: ACS Chemical Biology, Science Daily, BBC