Quenching corrinoid-based interactions in a model bacterial coculture.

Microbial community structure is driven, in part, by the metabolic interdependencies of resident microbes. Thus, manipulating specific metabolic interactions represents an attractive way to both understand how microbial communities perform complex functions and alter them for therapeutic or environmental effects. However, it is not yet possible to control the availability of those metabolites produced by some members of the community that are required by others. Here, we report the development of a metabolite "quenching" strategy that disrupts a specific metabolic interaction involving corrinoids, the vitamin B12 family of cofactors, by applying a high-affinity corrinoid-binding protein, BtuG, to bacteria engaged in corrinoid cross-feeding. Using a model coculture composed of Sinorhizobium meliloti, a bacterium that produces a corrinoid (cobalamin), and an Escherichia coli strain engineered to be corrinoid-dependent, we demonstrate corrinoid quenching by sequestration of extracellular corrinoid, leading to inhibition of corrinoid-dependent growth. This work establishes a strategy to selectively block microbial interactions that may be more broadly applied to dissecting community structure and function. We expect that applying high-affinity "molecular sponges" to quench nutrient sharing will allow for the identification of key nutrients that structure microbial communities and potentiate precision microbiome manipulation strategies.