Dataset Information

Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach.

ABSTRACT: 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).

SUBMITTER: Fernandez-Garcia M

PROVIDER: S-EPMC7199213 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach.

Fernández-García Miguel M Rey-Stolle Fernanda F Boccard Julien J Reddy Vineel P VP García Antonia A Cumming Bridgette M BM Steyn Adrie J C AJC Rudaz Serge S Barbas Coral C

Journal of proteome research 20200423 5

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 multivari ...[more]

PMID: 32285670

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Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach.

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Comprehensive Examination of the Mouse Lung Metabolome Following <i>Mycobacterium tuberculosis</i> Infection Using a Multiplatform Mass Spectrometry Approach.

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Dataset Information

Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach.

Publications

Comprehensive Examination of the Mouse Lung Metabolome Following &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; Infection Using a Multiplatform Mass Spectrometry Approach.

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OmicsDI is part of the ELIXIR infrastructure

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Comprehensive Examination of the Mouse Lung Metabolome Following <i>Mycobacterium tuberculosis</i> Infection Using a Multiplatform Mass Spectrometry Approach.