Identification of specific metabolic capacities associated with major extraintestinal pathogenic Escherichia coli lineages

Bacterial niche colonization relies on multiple factors, among which the metabolic capacity to utilize specific substrates is pivotal, especially within complex microbiota where nutrient competition is intense. Escherichia coli, a gut commensal of humans and vertebrates, is also an opportunistic pathogen responsible for both intestinal and extraintestinal infections, including bloodstream infections (BSI). To identify metabolic specificities of pathogenic strains that could explain the emergence and success of major clones, we leveraged a well-characterized dataset of 1,498 genomes from both commensal and extraintestinal pathogenic epidemiologically relevant French isolates. Using a pangenomic framework, we conducted a large-scale analysis of metabolic pathways. Although metabolism was far more conserved than gene content, we found substantial metabolic diversity across the species, with over 50% of pathways being variable, mainly involving biosynthetic and degradation processes. Phylogeny had a major impact on metabolic profiles, while no specific pathway was associated with lifestyle (commensal vs. pathogenic) or BSI portal of entry. However, we identified clone-specific metabolic capacities. For example, pathways involved in 5-deoxynucleoside recycling were enriched in the major extraintestinal pathogen (ExPEC) clone STc69. In phylogroup B2, several clone-specific pathways enabled degradation of plant-derived compounds. Notably, detailed analysis of the D-apiose degradation revealed a functional pathway strongly associated with the STc131 and STc14 pandemic clones. Overall, our study highlights multiple lineage-specific metabolic capacities that may contribute to the ecological success and dissemination of most prevalent ExPEC clones. ImportanceAccording to the nutrient-niche hypothesis, both commensal and pathogenic E. coli strains must exploit distinct substrates to grow and persist in their primary habitat alongside resident microbiota. Such niche differentiation also occurs between E. coli populations competing within the same environment and partly explains the stable coexistence of strains in the gut. With this in mind, we search for specific associations between metabolic pathways and strain origin. However, metabolic profiles were predominantly shaped by phylogeny, reflecting the species clonal structure and the close link between phylogenetic background and lifestyle. Among the lineage-specific determinants, we identified several pathways associated with worldwide spread clones responsible for bloodstream infections, supporting the existence of clone-specific strategies for niche adaptation.