Agapova, Aleksandra Serafini, Agnese Petridis, Michael Hunt, Debbie M Garza-Garcia, Acely Sohaskey, Charles D de Carvalho, Luiz Pedro Sório Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis 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. Mycobacterium tuberculosis;amino acid metabolism;infectious disease;metabolomics;microbiology;nitrogen metabolism;stable isotope labelling;Carvalho FC001060;Biochemistry and Cell Biology 2019-11-18
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