Martin Keller

Cultivating the uncultured

The recent application of molecular phylogeny to environmental samples has resulted in the discovery of an abundance of unique and previously unrecognized microorganisms. The vast majority of this microbial diversity has proved refractory to cultivation. Here, we describe a universal method that provides access to this immense reservoir of untapped microbial diversity. This technique combines encapsulation of cells in gel microdroplets for massively parallel microbial cultivation under low nutrient flux conditions, followed by flow cytometry to detect microdroplets containing microcolonies. The ability to grow and study previously uncultured organisms in pure culture will enhance our understanding of microbial physiology and metabolic adaptation and will provide new sources of microbial metabolites. We show that this technology can be applied to samples from several different environments, including seawater and soil.

Tapping into microbial diversity

Even though significant advances have been made in understanding microbial diversity, most microorganisms are still only characterized by molecular fingerprints and have resisted cultivation. Many different approaches have been developed to overcome the problems associated with cultivation of microorganisms because one obvious benefit would be the opportunity to investigate the previously inaccessible resources that these microorganisms potentially harbour.

New Methods to Access Microbial Diversity for Small Molecule Discovery

Natural-product-derived drugs are a major portion of the total number of approved drugs in the antibacterial area. The majority of bacteria and fungi in the environment is only known by molecular fingerprints and has resisted cultivation. Therefore, new methods have been developed to access this tremendous microbial diversity for the discovery of novel small molecules. These culture-dependent and -independent methods include a novel high-throughput cultivation technology as well as a recombinant approach to discover and express novel natural products.