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

ABSTRACT Bacterial niche colonization relies on multiple factors, among which the metabolic capacity to utilize specific substrates is pivotal. As a gut commensal of humans and other vertebrates acting as an intestinal and extraintestinal opportunistic pathogen, Escherichia coli faces such environmental pressures. We therefore aimed to identify (i) metabolic patterns associated with E. coli lifestyle (commensal versus extraintestinal pathogenic E. coli [ExPEC]) and (ii) ExPEC-specific metabolic features that could help explain the emergence and success of major pandemic clones. Using a pangenomic framework coupled with metabolic pathway prediction, we analyzed 1,498 well-characterized E. coli strains collected over 17 years in France, including adult commensal strains ( n = 370) and ExPEC strains involved in severe infections (bloodstream infections from various portals of entry and pneumonia) ( n = 1,128). Although metabolism was more conserved than gene content, substantial metabolic diversity was observed, with over 50% pathways being variable, mainly involving biosynthetic and degradation processes. No pathway was specifically associated with lifestyle; metabolic profiles primarily reflected phylogeny. However, several clone-specific metabolic capacities were identified. Some may support extraintestinal survival during infection, such as the 5’-deoxynucleoside recycling pathway enriched in the major ExPEC clone STc69 from phylogroup D. Conversely, in phylogroup B2, clone-specific pathways enabled the degradation of plant-derived compounds, potentially facilitating gut colonization through niche-defining nutrients. Notably, D-apiose degradation pathway analysis revealed a functional pathway strongly associated with the pandemic clones STc131 and STc14. Overall, these lineage-specific metabolic capacities may contribute to the ecological success and dissemination of dominant ExPEC clones. IMPORTANCE According to the nutrient-niche hypothesis, bacteria must exploit distinct substrates to grow and persist in their various habitats. Such niche differentiation is at play among the commensal and pathogenic E. coli populations. With this in mind, we search for specific associations between metabolic pathways and strain origin (commensal versus severe extraintestinal infections). 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.