(674b) Intracellular Metabolic Circuits Shape Intercellular Interactions in Multi-Species Microbial Games | AIChE

(674b) Intracellular Metabolic Circuits Shape Intercellular Interactions in Multi-Species Microbial Games

Authors 

Zomorrodi, A. R. - Presenter, Boston University
Segrè, D., Boston University
Metabolite exchanges in microbial communities give rise to ecological interaction networks that govern ecosystem diversity and stability. These exchanges are mediated by complex intracellular pathways thus raising the question of whether ecological interactions are inferable from genomes. We address this question by integrating genome-scale models of metabolism, to compute the fitness of interacting microbes, with evolutionary game theory, which uses these fitness values to infer evolutionarily stable interactions in multi-species microbial “games”. After validating our approach using data on sucrose hydrolysis by S. cerevisiae, we performed over 80,000 in silico experiments to evaluate the rise of unidirectional and cross-feeding metabolic dependencies in populations of Escherichia coli secreting 189 amino acid pairs. We found that, despite the diversity of exchanged amino acids, most pairs conform to general patterns of inter-species interactions. However, several amino acid pairs deviate from these patterns due to pleiotropy and epistasis in metabolic pathways. We also identified evolutionary paths that could lead to obligate cross-feeding by performing targeted in silico invasion experiments,. Overall, our study provides mechanistic insights into the rise of evolutionarily stable inter-species dependencies, with important implications for biomedicine and microbiome engineering.