{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T11:41:26Z","timestamp":1778326886501,"version":"3.51.4"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To investigate metabolic markers linked to <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>M<\/jats:italic>. <jats:italic>tb)<\/jats:italic> in the cerebrospinal fluid (CSF) of a South African cohort of paediatric tuberculous meningitis (TBM).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Targeted proton magnetic resonance (<jats:sup>1<\/jats:sup>H-NMR) spectroscopy and two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) metabolomics approaches were used to evaluate <jats:italic>M<\/jats:italic>. <jats:italic>tb<\/jats:italic>-linked metabolites in the CSF of 21 definite cases of TBM and 25 control cases. Uni- and multivariate statistical analyses were performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Four statistically significant metabolites were identified to discriminate TBM cases from controls. Mannose and arabinose were found at lower concentrations in the TBM group. Nonanoic acid and propanoic acid were found in higher concentrations in the definite TBM group.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We identified the novel presence of nonanoic acid for the first time as a <jats:italic>M<\/jats:italic>. <jats:italic>tb<\/jats:italic>-linked marker in the CSF of cases of TBM, possibly as a degradation product of the <jats:italic>M<\/jats:italic>. <jats:italic>tb<\/jats:italic> cell wall. Propanoic acid can be related to perturbed brain neuro-energetics and neuro-inflammation in TBM cases and is likely a host-response metabolite. Mannose and arabinose\u2013supposed surrogates for lipoarabinomannan, a component of the <jats:italic>M<\/jats:italic>. <jats:italic>tb<\/jats:italic> cell wall\u2013were not reliable markers for <jats:italic>M<\/jats:italic>. <jats:italic>tb<\/jats:italic>. Further research should focus on the analysis of fatty acids in the CSF of patients with TBM.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0314854","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T18:30:33Z","timestamp":1734460233000},"page":"e0314854","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeted metabolomics investigation of metabolic markers of Mycobacterium tuberculosis in the cerebrospinal fluid of paediatric patients with tuberculous meningitis"],"prefix":"10.1371","volume":"19","author":[{"given":"Victory","family":"Samuel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-8443","authenticated-orcid":true,"given":"Regan","family":"Solomons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-5768","authenticated-orcid":true,"given":"Shayne","family":"Mason","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"issue":"1","key":"pone.0314854.ref001","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1542\/peds.2008-1353","article-title":"Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the western cape of South Africa","volume":"123","author":"G.T. 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