Bacterial Fight Club Produces New Metabolites

When bacteria are forced to face off against each other, the fight can induce them to produce metabolites they don’t make when they’re hanging out by themselves. To study this phenomenon, Brian O. Bachmann, John A. McLean, and coworkers at Vanderbilt University pit bacterial strains against each other two at a time in cocultures to find new polyketide natural products for potential drugs (ACS Chem. Biol. 2015, DOI: 10.1021/acschembio.5b00001). The researchers analyze the coculture extracts with liquid chromatography-ion mobility mass spectrometry. Then they process the data with an algorithm that organizes spectral features according to the way they vary across coculture conditions to create a visually interpretable heat map. By subtracting the monoculture feature maps from the coculture feature maps, the researchers identify metabolites that are produced only in coculture. When the Vanderbilt team cocultured a Nocardiopsis strain with other kinds of bacteria, almost 14% of the detected metabolites were produced only in cocultures. In addition, the bacteria produced different metabolites in response to different sparring partners. One metabolite from a coculture of Nocardiopsis ΔApoS and Rhodococcus wratislaviensis—dubbed ciromicin A—contains an unusual pyrrolidinol substructure and is toxic to cancer cells.