Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis.
Aleksandra AgapovaAgnese SerafiniMichael PetridisDebbie M HuntAcely Garza-GarciaCharles D SohaskeyLuiz Pedro Sorio de CarvalhoPublished in: eLife (2019)
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 a product of evolution in the human host.
Keyphrases
- mycobacterium tuberculosis
- amino acid
- mass spectrometry
- pulmonary tuberculosis
- drinking water
- hiv aids
- high resolution
- liquid chromatography
- hepatitis c virus
- optical coherence tomography
- human immunodeficiency virus
- high performance liquid chromatography
- drug induced
- electronic health record
- antiretroviral therapy
- capillary electrophoresis
- tandem mass spectrometry