Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid
Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Background: The defining feature of the cerebrospinal fluid (CSF) collected from infants and children with
tuberculous meningitis (TBM), derived from an earlier untargeted nuclear magnetic resonance (NMR) metabolomics
study, was highly elevated lactic acid. Undetermined was the contribution from host response (L-lactic acid) or of
microbial origin (D-lactic acid), which was set out to be determined in this study.
Methods: In this follow-up study, we used targeted ultra-performance liquid chromatography–electrospray
ionization–tandem mass spectrometry (UPLC–ESI–MS/MS) to determine the ratio of the L and D enantiomers of
lactic acid in these CSF samples.
Results: Here we report for the first time that the lactic acid observed in the CSF of confirmed TBM cases was in
the L-form and solely a response from the host to the infection, with no contribution from any bacteria. The
significance of elevated lactic acid in TBM appears to be that it is a crucial energy substrate, used preferentially over
glucose by microglia, and exhibits neuroprotective capabilities.
Conclusion: These results provide experimental evidence to support our conceptual astrocyte–microglia lactate
shuttle model formulated from our previous NMR-based metabolomics study — highlighting the fact that lactic
acid plays an important role in neuroinflammatory diseases such as TBM. Furthermore, this study reinforces our
belief that the determination of enantiomers of metabolites corresponding to infectious diseases is of critical
importance in substantiating the clinical significance of disease markers.
Description
CITATION: Mason, S., et al. 2016. Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid. BMC Infectious Diseases, 6:251, doi:10.1186/s12879-016-1597-9.
The original publication is available at http://bmcinfectdis.biomedcentral.com
The original publication is available at http://bmcinfectdis.biomedcentral.com
Keywords
Liquid chromatography, Meninges -- Tuberculosis, Cerebrospinal fluid, Lactic acid -- Biotechnology, Enantiomers -- Biotechnology
Citation
Mason, S., et al. 2016. Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid. BMC Infectious Diseases, 6:251, doi:10.1186/s12879-016-1597-9