Flexible nitrogen utilisation by the metabolic generalist pathogen <i>Mycobacterium tuberculosis</i>.

Abstract

Bacterial metabolism is fundamental to survival and pathogenesis. We explore how <i>Mycobacterium tuberculosis</i> 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 <i>M. tuberculosis</i>, 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 <i>M. tuberculosis</i>, 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 <i>M. tuberculosis</i> and reveals a flexible metabolic network with characteristics that are likely a product of evolution in the human host.