Abstract

Conflict and cooperation between bacterial species drive the composition and function of microbial communities. Stability of these emergent properties will be influenced by the degree to which species' interactions are robust to genetic perturbations. We use genome-scale metabolic modeling to computationally analyze the impact of genetic changes when Escherichia coli and Salmonella enterica compete, or cooperate. We systematically knocked out in silico each reaction in the metabolic network of E. coli to construct all 2583 mutant stoichiometric models. Then, using a recently developed multi-scale computational framework, we simulated the growth of each mutant E. coli in the presence of S. enterica. The type of interaction between species was set by modulating the initial metabolites present in the environment. We found that the community was most robust to genetic perturbations when the organisms were cooperating. Species ratios were more stable in the cooperative community, and community biomass had equal variance in the two contexts. Additionally, the number of mutations that have a substantial effect is lower when the species cooperate than when they are competing. In contrast, when mutations were added to the S. enterica network the system was more robust when the bacteria were competing. These results highlight the utility of connecting metabolic mechanisms and studies of ecological stability. Cooperation and conflict alter the connection between genetic changes and properties that emerge at higher levels of biological organization.

Highlights

  • Microbes often lead highly social lifestyles, engaging in interactions that span the gamut from cooperation to conflict (Mitri and Foster, 2013)

  • The community reached a final biomass of 2.85 × 10−6 g, and the frequency of E. coli increased to 80.7%

  • In S. enterica, Cooperation Stabilizes Species Ratios but Not Total Biomass To test the generality of our findings, we examined the impact of knocking out each reaction in the S. enterica model and again simulating growth of each mutant when competing and cooperating with E. coli

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Summary

Introduction

Microbes often lead highly social lifestyles, engaging in interactions that span the gamut from cooperation to conflict (Mitri and Foster, 2013). These interactions determine the composition and function of microbial systems, and influence communities that are critical for both natural and applied processes. The dynamics of species interactions are intimately connected to the behavior of physiological networks inside of cells. It is unclear how sensitive species interactions are to intracellular perturbations and vice versa. How do species interactions influence the physiological robustness of species? How robust to mutation are emergent community properties when species are competing vs. when they are cooperating? And how do species interactions influence the physiological robustness of species?

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