Abstract
BACKGROUND: Tuberculous meningitis (TBM) is a disease caused by Mycobacterium tuberculosis (M. tb) infection of the brain. Alkanes and other volatile organic compounds (VOCs) are biologically important metabolites that are used by infectious mycobacteria species for growth and survival strategies. OBJECTIVE: This study investigated the altered alkanes and other VOCs in the urine from paediatric cases with TBM. METHOD: We used untargeted gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) to analyse and compare all volatile, underivatised compounds present in the urine from 27 confirmed cases of paediatric TBM over a treatment period of six months, as well as a control group (n = 13). RESULT: Four elevated alkanes (pentadecane, 5,7-dimethyl-undecane, 4,7-dimethyl-undecane, and 2,6-dimethyl-undecane), three alkenes (decreased 2,5-dimethyl-2-hexene and 4,4-dimethyl-1-pentene, and increased 3-methoxy-1-pentene), and three other VOCs of biological interest (decreased 2-butenoic acid methyl ester and 3-heptanone, and increased 2-pyrrolidinone) were identified as statistically significant. These volatile compounds remained perturbed during the TBM treatment. CONCLUSION: This study discovered new systemic metabolic information about M. tb in the host and the role of alkanes and VOCs in the potential persistence of M. tb. We demonstrate the value of targeting alkanes and other VOCs for future metabolomics studies of M. tb.