Targeted metabolomics investigation of metabolic markers of Mycobacterium tuberculosis in the cerebrospinal fluid of paediatric patients with tuberculous meningitis

• Published in: PloS one 2024-12, Vol.19 (12), p.e0314854
• Main Authors: Samuel, Victory, Solomons, Regan, Mason, Shayne
• Format: Article
• Language: English
• Subjects: Acids; Adolescent; Analysis; Arabinose; Arabinose - cerebrospinal fluid; Arabinose - metabolism; Biology and Life Sciences; Biomarkers - cerebrospinal fluid; Brain research; Care and treatment; Case-Control Studies; Cell walls; Cerebrospinal fluid; Child; Child, Preschool; Children; Diagnosis; Diseases; Ethics; Female; Gas chromatography; Gas Chromatography-Mass Spectrometry; HIV; Human immunodeficiency virus; Humans; Infant; Magnetic resonance; Male; Mannose; Mannose - cerebrospinal fluid; Mannose - metabolism; Mass spectrometry; Mass spectroscopy; Medicine and Health Sciences; Meningitis; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Mortality; Mycobacterium tuberculosis; NMR; Nuclear magnetic resonance; Pediatrics; Physical Sciences; Potassium; Propionic acid; Proton magnetic resonance; Scientific imaging; Spectroscopy; Statistical analysis; Tomography; Tuberculosis; Tuberculosis, Meningeal - cerebrospinal fluid; Tuberculosis, Meningeal - microbiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0314854

To investigate metabolic markers linked to Mycobacterium tuberculosis (M. tb) in the cerebrospinal fluid (CSF) of a South African cohort of paediatric tuberculous meningitis (TBM). Targeted proton magnetic resonance (1H-NMR) spectroscopy and two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) metabolomics approaches were used to evaluate M. tb-linked metabolites in the CSF of 21 definite cases of TBM and 25 control cases. Uni- and multivariate statistical analyses were performed. 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. We identified the novel presence of nonanoic acid for the first time as a M. tb-linked marker in the CSF of cases of TBM, possibly as a degradation product of the M. tb 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-supposed surrogates for lipoarabinomannan, a component of the M. tb cell wall-were not reliable markers for M. tb. Further research should focus on the analysis of fatty acids in the CSF of patients with TBM.