Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis

Abstract
Data availability
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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).

The following data sets were generated

(2019) Metabolomics data from Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis
Zenodo, doi:10.5281/zenodo.2551162.

https://zenodo.org/record/2551162#.XFLBAhn7RTY

Article and author information

Author details

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.
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.
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.
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.
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.

"This ORCID iD identifies the author of this article:" 0000-0003-0307-0138
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.
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.

"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.

Copyright

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.