{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:58:13Z","timestamp":1781272693630,"version":"3.54.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antibiotic-resistant bacterial infections remain a major global health threat, particularly in hospital settings. Standard antimicrobial susceptibility testing provides essential clinical information, but it does not fully capture pathogen metabolic adaptation under host-like conditions. Integrating isolate whole-genome sequencing with metabolomics may help prioritize condition-associated metabolic signatures linked to bacterial physiology and antibiotic response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a secondary integrative re-analysis of publicly available isolate whole-genome sequencing and matched metabolomics datasets from\n                      <jats:italic>Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus<\/jats:italic>\n                      , and\n                      <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                      cultured under RPMI and human serum conditions. Genome assemblies were assessed by quality metrics, fastANI, functional annotation, antimicrobial resistance gene screening, virulence-factor analysis, and KEGG profiling. Metabolomics data were analyzed using PCA, OPLS-DA, KEGG enrichment, and ROC analysis for exploratory feature prioritization. Candidate metabolites were further evaluated in\n                      <jats:italic>Klebsiella quasipneumoniae<\/jats:italic>\n                      ATCC 700603 cultured under RPMI or heat-inactivated human serum conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Metabolomic profiles showed condition-associated separation between RPMI and serum samples, with the most consistent serum-associated signature observed in\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      . KEGG enrichment prioritized amino acid metabolism, particularly valine, leucine and isoleucine biosynthesis and alanine, aspartate and glutamate metabolism. l-aspartic acid, l-isoleucine, l-leucine, and l-valine showed strong within-dataset discriminatory performance in\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      . Experimental validation showed that serum exposure reduced\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      growth and viable bacterial burden, increased cell-associated levels of these amino acids, and elevated meropenem and ciprofloxacin MIC-like inhibitory endpoints under serum-conditioned assay conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This integrative re-analysis identified serum-associated amino acid remodeling as a prominent feature of host-like adaptation in Klebsiella. These findings provide candidate metabolic signatures for future mechanistic validation and suggest that serum exposure is associated with growth restriction and reduced antibiotic susceptibility under host-like conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1734675","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:13:25Z","timestamp":1781270005000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-informed metabolomic re-analysis identifies serum-associated amino acid signatures in sepsis-associated bacterial pathogens"],"prefix":"10.3389","volume":"13","author":[{"given":"Min","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"West China School of Nursing, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"West China School of Nursing, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Hemodialysis Center, Chengdu First People's Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"West China School of Nursing, Sichuan University","place":["Chengdu, Sichuan, 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