MEAPS: A method to discover bioactive compounds generated by gut microbes

Unmet Need

Microbial communities play important roles in environmental, animal, and human health. In humans, beneficial bacteria living within the intestinal tract can promote gut development, balance immunity, and enhance nutrient metabolism. Alternatively, colonization with deleterious microbial species predicts poor gut health and increases the risk of obesity and metabolic disorders. Despite their importance to the health of their host, most intestinal microbes remain uncharacterized because they are not amenable to genetic manipulation and subsequent experimentation. As a result, the specific genes and molecules microbes use to alter host physiology are largely undiscovered. Therefore, there is a need for a non-genetic method to characterize the genes controlling traits of certain microbes within a community.

Technology

Duke inventors have developed a method called Mutational Enrichment Analysis post phenotypic selection (MEAPS) to characterize the genes and bioactive compounds responsible for specific traits in microbes. This is intended to be used for the discovery of compounds for medical applications, additional drug targets to control bacterial infections, and new approaches to control dysbiosis of microbiomes. Specifically, MEAPS utilizes chemical mutagenesis, phenotypic selection, and population-based genome sequencing to identify genes associated with bacterial traits without species-specific genetic tools. This has been demonstrated in a proof-of-principle study that successfully characterized the relevant genes associated with motility in Exiguobacterium acetylicum, a poorly characterized gut bacterium.

Other Applications

This technology could also be used for livestock and industrial applications, which often utilize microbial compounds.

Advantages

• Enables identification of genes responsible for certain traits even when the microbe is rare, understudied, or genetically intractable

• Allows for functional characterization of genes identified, giving additional information about how the discovered gene contributes to the trait of interest

• The MEAPS method can be applied to any culturable bacterial species