1. Microbiology and Infectious Disease
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Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis

  1. Aleksandra Agapova
  2. Agnese Serafini
  3. Michael Petridis
  4. Debbie M Hunt
  5. Acely Garza-Garcia
  6. Charles D Sohaskey
  7. Luiz Pedro Sorio de Carvalho  Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. Department of Veterans Affairs Medical Center, United States
Research Article
  • Cited 10
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Cite this article as: eLife 2019;8:e41129 doi: 10.7554/eLife.41129

Abstract

Bacterial metabolism is fundamental to survival and pathogenesis. We explore how Mycobacterium tuberculosis utilises amino acids as nitrogen sources, using a combination of bacterial physiology and stable isotope tracing coupled to mass spectrometry metabolomics methods. Our results define core properties of the nitrogen metabolic network from M. tuberculosis, such as: (i) the lack of homeostatic control of certain amino acid pool sizes; (ii) similar rates of utilisation of different amino acids as sole nitrogen sources; (iii) improved nitrogen utilisation from amino acids compared to ammonium; and (iv) co-metabolism of nitrogen sources. Finally, we discover that alanine dehydrogenase, is involved in ammonium assimilation in M. tuberculosis, in addition to its essential role in alanine utilisation as a nitrogen source. This study represents the first in-depth analysis of nitrogen source utilisation by M. tuberculosis and reveals a flexible metabolic network with characteristics that are likely product of evolution in the human host.

Article and author information

Author details

  1. Aleksandra Agapova

    Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Agnese Serafini

    Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael Petridis

    Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Debbie M Hunt

    Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Acely Garza-Garcia

    Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0307-0138
  6. Charles D Sohaskey

    Tuberculosis Research Lab, Department of Veterans Affairs Medical Center, Long Beach, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Luiz Pedro Sorio de Carvalho

    Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom
    For correspondence
    luiz.carvalho@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2875-4552

Funding

Wellcome (104785/B/14/Z)

  • Aleksandra Agapova
  • Agnese Serafini
  • Michael Petridis
  • Luiz Pedro Sorio de Carvalho

Wellcome (Francis Crick Institute Core funding (10060))

  • Debbie M Hunt
  • Acely Garza-Garcia
  • Luiz Pedro Sorio de Carvalho

Medical Research Council (Francis Crick Institute Core funding (10060))

  • Debbie M Hunt
  • Acely Garza-Garcia
  • Luiz Pedro Sorio de Carvalho

Cancer Research UK (Francis Crick Institute Core funding (10060))

  • Debbie M Hunt
  • Acely Garza-Garcia
  • Luiz Pedro Sorio de Carvalho

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Received: August 15, 2018
  2. Accepted: January 22, 2019
  3. Accepted Manuscript published: January 31, 2019 (version 1)
  4. Version of Record published: February 4, 2019 (version 2)

Copyright

© 2019, Agapova et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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