Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach.
- Fernández-García M Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28660, Spain.
- Rey-Stolle F Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28660, Spain.
- Boccard J School of Pharmaceutical Sciences, University of Lausanne and University of Geneva, Geneva 1211, Switzerland.
- Reddy VP Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, United States.
- García A Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28660, Spain.
- Cumming BM Africa Health Research Institute, Durban 4001, South Africa.
- Steyn AJC Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, United States.
- Rudaz S School of Pharmaceutical Sciences, University of Lausanne and University of Geneva, Geneva 1211, Switzerland.
- Barbas C Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28660, Spain.
- 2020-04-15
Published in:
- Journal of proteome research. - 2020
data fusion
functional metabolomics
metabolomics
multiplatform metabolomics
pulmonary tuberculosis
tuberculosis
tuberculosis progression
English
The mechanisms whereby Mycobacterium tuberculosis (Mtb) rewires the host metabolism in vivo are surprisingly unexplored. Here, we used three high-resolution mass spectrometry platforms to track altered lung metabolic changes associated with Mtb infection of mice. The multiplatform data sets were merged using consensus orthogonal partial least squares-discriminant analysis (cOPLS-DA), an algorithm that allows for the joint interpretation of the results from a single multivariate analysis. We show that Mtb infection triggers a temporal and progressive catabolic state to satisfy the continuously changing energy demand to control infection. This causes dysregulation of metabolic and oxido-reductive pathways culminating in Mtb-associated wasting. Notably, high abundances of trimethylamine-N-oxide (TMAO), produced by the host from the bacterial metabolite trimethylamine upon infection, suggest that Mtb could exploit TMAO as an electron acceptor under anaerobic conditions. Overall, these new pathway alterations advance our understanding of the link between Mtb pathogenesis and metabolic dysregulation and could serve as a foundation for new therapeutic intervention strategies. Mass spectrometry data has been deposited in the Metabolomics Workbench repository (data-set identifier: ST001328).
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1021/acs.jproteome.9b00868
- PMID 32285670
- Persistent URL
- https://sonar.ch/global/documents/149754
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