{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:21Z","timestamp":1783574121737,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Objective<\/jats:title>\n \n Escherichia coli<\/jats:italic>\n and\n Klebsiella pneumoniae<\/jats:italic>\n are major Gram-negative pathogens causing bloodstream infection (BSI) and sepsis, but their plasma host-response patterns remain incompletely characterized. This study aimed to explore shared and pathogen-associated proteomic and metabolomic features in\n E. coli<\/jats:italic>\n BSI and\n K. pneumoniae<\/jats:italic>\n BSI.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We performed plasma proteomic and metabolomic profiling in 100 participants, including patients with\n E. coli<\/jats:italic>\n BSI (n = 26),\n K. pneumoniae<\/jats:italic>\n BSI (n = 15), blood culture-negative sepsis (NegBC, n = 29), and healthy controls (HC, n = 30). Differential molecular analyses were performed with additional adjustment for baseline clinical covariates where applicable. Downstream GO, KEGG, PPI, and protein\u2013metabolite network analyses were based on molecules that remained significant after covariate adjustment. A leakage-free internal validation framework was used to construct an exploratory plasma proteome-based model for distinguishing\n E. coli<\/jats:italic>\n BSI from non-\n E. coli<\/jats:italic>\n sepsis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Both\n E. coli<\/jats:italic>\n BSI and\n K. pneumoniae<\/jats:italic>\n BSI showed prominent coagulation-immune alterations involving complement\/coagulation-related pathways.\n E. coli<\/jats:italic>\n BSI showed a more evident platelet-centered immunometabolic pattern, particularly relative to NegBC, whereas\n K. pneumoniae<\/jats:italic>\n BSI showed coagulation-immune activation coupled with lipid and broader metabolic remodeling. In the direct comparison between\n E. coli<\/jats:italic>\n BSI and\n K. pneumoniae<\/jats:italic>\n BSI, no proteins remained significantly different after covariate adjustment, whereas metabolomic differences persisted, involving glycine, serine and threonine metabolism, terpenoid backbone biosynthesis, apoptosis, and folate biosynthesis. An exploratory\n E. coli<\/jats:italic>\n BSI model based on FCGR3A, COPS3, NT5C3A, and ADO showed preliminary discrimination between\n E. coli<\/jats:italic>\n BSI and non-\n E. coli<\/jats:italic>\n sepsis in leakage-free internal validation (AUC\u00a0=\u00a00.806, 95% CI: 0.706\u20130.906).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Plasma multi-omics suggested shared thromboinflammatory features and partially distinct platelet-associated and metabolic patterns in\n E. coli<\/jats:italic>\n BSI and\n K. pneumoniae<\/jats:italic>\n BSI. However, findings involving direct pathogen comparison and the\n K. pneumoniae<\/jats:italic>\n BSI cohort should be interpreted cautiously because of baseline clinical heterogeneity and limited sample size. The candidate diagnostic model remains exploratory and requires external validation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1873717","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:22:05Z","timestamp":1783570925000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma multi-omics reveals pathogen-associated mechanisms and diagnostic signatures in Escherichia coli and Klebsiella pneumoniae bloodstream infections"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuxin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xian","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunjie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianpeng","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanglin","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qionglan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Third Hospital of Mianyang, Sichuan Mental Health Center","place":["Mianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136114","article-title":"Immunothrombosis in sepsis: cellular crosstalk, molecular triggers, and therapeutic opportunities\u2014A review","volume":"26","author":"Aklilu","year":"2025","journal-title":"Int. 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