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Melioidosis, infection with the gram-negative bacterium Burkholderia pseudomallei, is a frequent cause of fatal sepsis in endemic tropical regions such as Southeast Asia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate whether plasma metabolomics would identify biological pathways specific to melioidosis and yield clinically meaningful biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a comprehensive approach, differential enrichment of plasma metabolites and pathways was systematically evaluated in individuals selected from a prospective cohort of patients hospitalized in rural Thailand with infection. Statistical and bioinformatics methods were used to distinguish metabolomic features and processes specific to patients with melioidosis and between fatal and nonfatal cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Metabolomic profiling and pathway enrichment analysis of plasma samples from patients with melioidosis (n\u2009=\u2009175) and nonmelioidosis infections (n\u2009=\u200975) revealed a distinct immuno-metabolic state among patients with melioidosis, as suggested by excessive tryptophan catabolism in the kynurenine pathway and significantly increased levels of sphingomyelins and ceramide species. We derived a 12-metabolite classifier to distinguish melioidosis from other infections, yielding an area under the receiver operating characteristic curve of 0.87 in a second validation set of patients. Melioidosis nonsurvivors (n\u2009=\u200994) had a significantly disturbed metabolome compared with survivors (n\u2009=\u200981), with increased leucine, isoleucine, and valine metabolism, and elevated circulating free fatty acids and acylcarnitines. A limited eight-metabolite panel showed promise as an early prognosticator of mortality in melioidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Melioidosis induces a distinct metabolomic state that can be examined to distinguish underlying pathophysiological mechanisms associated with death. A 12-metabolite signature accurately differentiates melioidosis from other infections and may have diagnostic applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202207-1349oc","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T17:06:33Z","timestamp":1696871193000},"page":"288-298","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":10,"title":["Plasma Metabolomics Reveals Distinct Biological and Diagnostic Signatures for Melioidosis"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1561-6871","authenticated-orcid":false,"given":"Lu","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Biostatistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6727-3404","authenticated-orcid":false,"given":"Viriya","family":"Hantrakun","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prapit","family":"Teparrukkul","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gumphol","family":"Wongsuvan","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taniya","family":"Kaewarpai","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adul","family":"Dulsuk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-1171","authenticated-orcid":false,"given":"Nicholas P. J.","family":"Day","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7038-1844","authenticated-orcid":false,"given":"Rozenn N.","family":"Lemaitre","sequence":"additional","affiliation":[{"name":"Cardiovascular Health Research Unit and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisara","family":"Chantratita","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit"},{"name":"Department of Microbiology and Immunology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7240-5320","authenticated-orcid":false,"given":"Direk","family":"Limmathurotsakul","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit"},{"name":"Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-3533","authenticated-orcid":false,"given":"Ali","family":"Shojaie","sequence":"additional","affiliation":[{"name":"Department of Biostatistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-4367","authenticated-orcid":false,"given":"Sina A.","family":"Gharib","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-7204","authenticated-orcid":false,"given":"T. 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