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As a gut commensal of humans and other vertebrates acting as an intestinal and extraintestinal opportunistic pathogen,\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      faces such environmental pressures. We therefore aimed to identify (i) metabolic patterns associated with\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      lifestyle (commensal versus extraintestinal pathogenic\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      [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\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      strains collected over 17 years in France, including adult commensal strains (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 370) and ExPEC strains involved in severe infections (bloodstream infections from various portals of entry and pneumonia) (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\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\u2019-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.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        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\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        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\u2019 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.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00421-25","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T20:41:28Z","timestamp":1772224888000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Identification of specific metabolic capacities associated with major extraintestinal pathogenic\n                    <i>Escherichia coli<\/i>\n                    lineages"],"prefix":"10.1128","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9092-8336","authenticated-orcid":true,"given":"Guilhem","family":"Royer","sequence":"first","affiliation":[{"name":"Unit\u00e9 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