Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis
- The Francis Crick Institute, United Kingdom
- Department of Veterans Affairs Medical Center, United States
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.
Data availability
Metabolomics data used on this study are available via Zenodo (DOI 10.5281/zenodo.2551162).
Article and author information
Author details
Acely Garza-Garcia
Luiz Pedro Sorio de Carvalho
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
- Bavesh D Kana, University of the Witwatersrand, South Africa
Version history
- Received: August 15, 2018
- Accepted: January 22, 2019
- Accepted Manuscript published: January 31, 2019 (version 1)
- 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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Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis
eLife 8:e41129.
https://doi.org/10.7554/eLife.41129
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