Specific Eco-evolutionary Contexts in the Mouse Gut Reveal Escherichia coli Metabolic Versatility

Abstract

Members of the gut microbiota are thought to experience strong competition for nutrients. However, how such competition shapes their evolutionary dynamics and depends on intraand interspecies interactions is poorly known. Here we tested the hypothesis that Escherichia coli evolution in the mouse gut is more predictable across hosts in absence of interspecies competition than in the presence of other microbial species. Supporting this hypothesis, we observed a specific genetic adaptation in lrp, a gene encoding a global regulator of amino acid metabolism, predictably selected in germ-free mice two weeks after mono-colonization. Analysis of gut metabolites established that the lpr mutations increase E. coli ability to compete for amino acids and identified serine and threonine as the metabolites preferentially consumed by E. coli in the mono-colonized mouse gut. Preference for serine consumption was further demonstrated by testing a set of mutants in vitro and in vivo that showed loss of advantage of a lrp mutant impaired in serine metabolism. Remarkably, the presence of a single additional member of the microbiota (Blautia coccoides) was enough to alter the gut metabolic profile and consequently the evolutionary path of E. coli. In this environment, the lrp mutations did not conferred advantage to E. coli and genes involved in anaerobic respiration were selected instead, recapitulating the ecoevolutionary context from mice with a complex microbiota. Together, these results highlight the metabolic plasticity of E. coli and its extreme evolutionary versatility, tailored to the specific ecology it experiences in the gut.

Mutation accumulation and horizontal gene transfer inEscherichia colicolonizing the gut of old mice

“…These markers allow rapid detection of evolutionary adaptation to the gut through the emergence and spread of new mutations within the focal newly colonizing strains. The short treatment with streptomycin is able to break colonization resistance, allowing the invader E. coli to colonize the mouse gut under a complex gut microbiota, which may harbor a resident E. coli strain [6] and can affect its evolutionary trajectories [7].…”

Evolutionary Approaches to Combat Antibiotic Resistance: Opportunities and Challenges for Precision Medicine

“…Moreover, bacteria are forced to interact with other microbes upon colonization or infection of the host. In the process, commensal microbes impact the eco-evolutionary dynamics by affecting traits under selection (61). For example, monocolonization of the mouse gut by E. coli can lead to predictable bacterial metabolic adaptations through the selection of mutations in genes related to amino acid metabolism, a process that is, however, altered by co-colonization with other microbes (61).…”

“…In the process, commensal microbes impact the eco-evolutionary dynamics by affecting traits under selection (61). For example, monocolonization of the mouse gut by E. coli can lead to predictable bacterial metabolic adaptations through the selection of mutations in genes related to amino acid metabolism, a process that is, however, altered by co-colonization with other microbes (61). Another example is colonization resistance, where presence of a complex residing microbial community can protect against pathogen infections (62).…”

Loss of RpoS results in attenuatedEscherichia colicolonization of human intestinal organoids and a competitive disadvantage within the germ-free mouse intestine

“…Historically the model systems available to study intestinal epithelial-microbe interactions consisted primarily of immortalized cell lines and animal models. For instance, germ-free mice have become the gold-standard for investigating host and microbial responses during the establishment of defined bacterial populations within the microbe-naïve gut (5)(6)(7)(8)(9)(10).…”

“…Indeed, while a number of factors contribute to bacterial intestinal colonization, the ability to compete for a limited number of nutritional niches is paramount for successful colonization of the gut(35,36). In addition, several studies have demonstrated that nutrient availability is the primary driver of E. coli colonization and adaptation within the murine gut(9,35,37). Thus, competition may increase the nutritional stress within the germ-free mouse intestine, though perhaps not to the same degree as that inherent to the HIO lumen.…”