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Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis

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posted on 18.11.2019 by Aleksandra Agapova, Agnese Serafini, Michael Petridis, Debbie M Hunt, Acely Garza-Garcia, Charles D Sohaskey, Luiz Pedro Sório de Carvalho
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.

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Crick (Grant ID: 10060, Grant title: Carvalho FC001060) Wellcome Trust (Grant ID: 104785/B/14/Z, Grant title: 104785/B/14/Z)

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