Emergence and self-organization of bacterial metabolism in consortia of cross-feeding bacteria

• Applicants: Professor Dr. Alexander Grünberger; Professor Dr. Christian Kost
• Subject Area: Microbial Ecology and Applied Microbiology ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 504072468

Microbial communities play key roles in many terrestrial and marine environments. These vital functions typically emerge from complex interactions among individual strains that - in combination - give rise to collective function at the community-level. However, thus far, it has been difficult to predict consortium-level properties from knowledge of its lower-level constituents. A likely explanation is that the focal interactions typically take place in spatially structured environments. The self-organization that results from these interactions is then determining growth of individual strains, thus also dictating community-level function. In this project, we address this issue by using the growth of consortia consisting of auxotrophic bacteria as a model. None of these strains can grow in isolation, yet their growth depends on the provisioning of essential amino acids from other, co-occurring strains. Previous work established that auxotrophic bacteria commonly form multicellular clusters that enhance the exchange of metabolites between cells. Thus, this project aims to predict community-level function (i.e., growth) from the bottom-up. For this, we will use nine bacterial genotypes (3 species, 3 amino acid auxotrophies) that will be cultivated in all possible pairwise and three-way combinations. First, we will characterize individual strains regarding their amino acid production level and - growth requirements. This data will be used to parametrize an individual-based model, which will then be employed to predict the growth of auxotrophic genotypes within multicellular aggregates. Second, we will verify the predictions of the model by analysing the growth of auxotrophic strains in multicellular aggregates as well as on a community-level. Spatial interactions among strains will be analysed by taking advantage of a previously developed microfluidic set-up and workflow. Finally, the predictive power of the newly developed statistical and individual-based model will be scrutinized by changing the underlying parameters via cultivating strains and consortia in different carbon sources. Performing the same analyses as before will allow to verify and refine the newly developed mechanistic framework. Taken together, by linking cell-level processes to community-level properties, this work will provide fundamental new insights into how the spatial self-organization within multicellular aggregates drives the emergence of collective function in bacterial consortia.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2389: Emergent Functions of Bacterial Multicellularity
• International Connection: Israel, Switzerland
• Cooperation Partners: Professorin Dr. Sigal Ben-Yehuda; Professor Knut Drescher, Ph.D.