PT  - JOURNAL ARTICLE
AU  - Aleksandra Agapova
AU  - Debbie M. Hunt
AU  - Michael Petridis
AU  - Acely Garza-Garcia
AU  - Charles D. Sohaskey
AU  - Luiz Pedro S. de Carvalho
TI  - Nitrogen utilisation by the metabolic generalist pathogen <em>Mycobacterium tuberculosis</em>
AID  - 10.1101/385278
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 385278
4099  - http://biorxiv.org/content/early/2018/08/05/385278.short
4100  - http://biorxiv.org/content/early/2018/08/05/385278.full
AB  - Bacterial metabolism is fundamental to pathogenesis and has a dominant effect on bacterial killing by antibiotics. Here we explore how Mycobacterium tuberculosis utilises amino acids as nitrogen sources, using a combination of bacterial physiology and stable isotope tracing coupled to liquid chromatography 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 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. This study represents the first in-depth analysis of nitrogen source utilisation by metabolic generatlist M. tuberculosis and reveals a flexible metabolic network with characteristics that are likely product of evolution in the human host.