OpenLB
Open Library of Bioscience
Advanced Search
eLife
01 31, 2019;8

Flexible nitrogen utilisation by the metabolic generalist pathogen .

Aleksandra Agapova, Agnese Serafini, Michael Petridis, Debbie M Hunt, Acely Garza-Garcia, Charles D Sohaskey, Luiz Pedro Sório de Carvalho
Author Information
  1. Aleksandra Agapova: Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom.
  2. Agnese Serafini: Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom.
  3. Michael Petridis: Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom.
  4. Debbie M Hunt: Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom.
  5. Acely Garza-Garcia: Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom. ORCID
  6. Charles D Sohaskey: Department of Veterans Affairs Medical Center, Long Beach, United States.
  7. Luiz Pedro Sório de Carvalho: Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom. ORCID
PMID: 30702426 DOI: 10.7554/eLife.41129

Abstract

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

Keywords

Mycobacterium tuberculosis amino acid metabolism infectious disease metabolomics microbiology nitrogen metabolism stable isotope labelling

References

J Bacteriol. 2000 Oct;182(20):5715-20 [PMID: 11004169]
Trends Microbiol. 2011 Jul;19(7):307-14 [PMID: 21561773]
Elife. 2019 Jan 31;8: [PMID: 30702426]
Lancet Infect Dis. 2018 Jul;18(7):e183-e198 [PMID: 29580819]
J Bacteriol. 1975 Aug;123(2):407-18 [PMID: 238954]
J Mol Microbiol Biotechnol. 2009;17(1):20-9 [PMID: 18824837]
Tuberculosis (Edinb). 2007 Jul;87(4):384-90 [PMID: 17303474]
J Bacteriol. 2008 Jul;190(14):4894-902 [PMID: 18469098]
Sci Signal. 2009 Mar 24;2(63):ra12 [PMID: 19318624]
Nat Microbiol. 2017 May 22;2:17084 [PMID: 28530656]
J Bacteriol. 2012 Mar;194(5):1045-54 [PMID: 22210765]
Nat Rev Microbiol. 2014 Nov;12(11):729-37 [PMID: 25244084]
BMC Genomics. 2015 Oct 19;16:821 [PMID: 26482235]
Proc Natl Acad Sci U S A. 1968 Sep;61(1):229-36 [PMID: 4972364]
Nature. 1998 Jun 11;393(6685):537-44 [PMID: 9634230]
Biochem J. 1987 Jun 15;244(3):565-70 [PMID: 3446176]
J Exp Med. 1999 May 3;189(9):1425-36 [PMID: 10224282]
Nat Chem Biol. 2006 Oct;2(10):529-30 [PMID: 16936719]
Nat Chem Biol. 2013 Nov;9(11):674-6 [PMID: 24077180]
PLoS Pathog. 2014 Feb 20;10(2):e1003928 [PMID: 24586151]
Mol Microbiol. 2004 Jun;52(6):1691-702 [PMID: 15186418]
Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):10008-13 [PMID: 26221021]
PLoS Pathog. 2017 May 17;13(5):e1006399 [PMID: 28545104]
Nat Rev Microbiol. 2009 Dec;7(12):845-55 [PMID: 19855401]
Chem Biol. 2010 Oct 29;17(10):1122-31 [PMID: 21035735]
Mol Microbiol. 2008 Dec;70(6):1408-23 [PMID: 19019160]
Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11320-5 [PMID: 23801751]
Mol Microbiol. 2015 Sep;97(6):1142-57 [PMID: 26077160]
Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1132-7 [PMID: 24395793]
Microbiology (Reading). 2006 Sep;152(Pt 9):2727-2734 [PMID: 16946267]
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6554-9 [PMID: 23576728]
Nat Rev Microbiol. 2018 Aug;16(8):496-507 [PMID: 29691481]
Infect Immun. 2000 May;68(5):2888-98 [PMID: 10768986]

Grants

  1. FC001060/Wellcome Trust
  2. Francis Crick Institute Core funding (10060)/Cancer Research UK
  3. Francis Crick Institute Core funding (10060)/Medical Research Council

MeSH Term

Alanine Dehydrogenase
Amino Acids
Ammonium Compounds
Kinetics
Metabolic Networks and Pathways
Mycobacterium tuberculosis
Nitrogen

Chemicals

Amino Acids
Ammonium Compounds
Alanine Dehydrogenase
Nitrogen
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

Similar Articles

Cited By