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Molecular microbiology
Sep, 2015;97 (6): 1142-57.

Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress.

Kerstin J Williams, Victoria A Jenkins, Geraint R Barton, William A Bryant, Nitya Krishnan, Brian D Robertson
Author Information
  1. Kerstin J Williams: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
  2. Victoria A Jenkins: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
  3. Geraint R Barton: Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, SW7 2AZ, UK.
  4. William A Bryant: Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, SW7 2AZ, UK.
  5. Nitya Krishnan: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
  6. Brian D Robertson: MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Imperial College London, London, SW7 2AZ, UK.
PMID: 26077160 DOI: 10.1111/mmi.13091

Abstract

A key component to the success of Mycobacterium tuberculosis as a pathogen is the ability to sense and adapt metabolically to the diverse range of conditions encountered in vivo, such as oxygen tension, environmental pH and nutrient availability. Although nitrogen is an essential nutrient for every organism, little is known about the genes and pathways responsible for nitrogen assimilation in M. tuberculosis. In this study we have used transcriptomics and chromatin immunoprecipitation and high-throughput sequencing to address this. In response to nitrogen starvation, a total of 185 genes were significantly differentially expressed (96 up-regulated and 89 down regulated; 5% genome) highlighting several significant areas of metabolic change during nitrogen limitation such as nitrate/nitrite metabolism, aspartate metabolism and changes in cell wall biosynthesis. We identify GlnR as a regulator involved in the nitrogen response, controlling the expression of at least 33 genes in response to nitrogen limitation. We identify a consensus GlnR binding site and relate its location to known transcriptional start sites. We also show that the GlnR response regulator plays a very different role in M. tuberculosis to that in non-pathogenic mycobacteria, controlling genes involved in nitric oxide detoxification and intracellular survival instead of genes involved in nitrogen scavenging.

References

  1. J Biol Chem. 2010 Oct 1;285(40):31037-45 [PMID: 20639578]
  2. Microb Pathog. 2008 Jan;44(1):71-7 [PMID: 17888619]
  3. Nat Chem Biol. 2013 Nov;9(11):674-6 [PMID: 24077180]
  4. BMC Genomics. 2011 Apr 04;12:175 [PMID: 21463507]
  5. Tuberculosis (Edinb). 2004;84(3-4):218-27 [PMID: 15207491]
  6. J Bacteriol. 2008 Jul;190(14):4894-902 [PMID: 18469098]
  7. BMC Genomics. 2013 May 04;14:301 [PMID: 23642041]
  8. Nature. 1998 Jun 11;393(6685):537-44 [PMID: 9634230]
  9. PLoS Pathog. 2014 Feb 20;10(2):e1003928 [PMID: 24586151]
  10. Nature. 2009 Jul 2;460(7251):98-102 [PMID: 19516256]
  11. J Biol Chem. 2004 Sep 17;279(38):40174-84 [PMID: 15247240]
  12. Infect Immun. 2007 Nov;75(11):5509-17 [PMID: 17785469]
  13. Tuberculosis (Edinb). 2007 Jul;87(4):384-90 [PMID: 17303474]
  14. J Exp Med. 2003 Sep 1;198(5):693-704 [PMID: 12953091]
  15. BMC Syst Biol. 2013 Mar 25;7:26 [PMID: 23531303]
  16. Infect Immun. 2008 Feb;76(2):717-25 [PMID: 18070897]
  17. Annu Rev Microbiol. 2003;57:155-76 [PMID: 12730324]
  18. Biochem Soc Trans. 2005 Feb;33(Pt 1):170-2 [PMID: 15667297]
  19. IUBMB Life. 2008 Oct;60(10):643-50 [PMID: 18493948]
  20. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):42-7 [PMID: 17190799]
  21. Mol Microbiol. 2005 Jun;56(5):1274-86 [PMID: 15882420]
  22. J Biol Chem. 2014 May 30;289(22):15413-25 [PMID: 24733389]
  23. Nat Chem Biol. 2007 Jan;3(1):60-8 [PMID: 17143269]
  24. Brief Bioinform. 2013 Mar;14(2):178-92 [PMID: 22517427]
  25. PLoS Pathog. 2011 Nov;7(11):e1002342 [PMID: 22072964]
  26. J Bacteriol. 2013 Oct;195(20):4592-9 [PMID: 23935045]
  27. FEMS Microbiol Lett. 2012 May;330(1):38-45 [PMID: 22356601]
  28. J Biol Chem. 2013 Oct 11;288(41):29987-99 [PMID: 23983123]
  29. Methods Mol Biol. 2012;802:305-22 [PMID: 22130889]
  30. Cell Rep. 2013 Nov 27;5(4):1121-31 [PMID: 24268774]
  31. Infect Immun. 2012 Aug;80(8):2771-9 [PMID: 22645285]
  32. Front Microbiol. 2011 May 13;2:105 [PMID: 21734908]
  33. Biochemistry. 2000 Nov 7;39(44):13450-61 [PMID: 11063581]
  34. J Bacteriol. 2008 Nov;190(21):7108-16 [PMID: 18689485]
  35. Stat Appl Genet Mol Biol. 2004;3:Article3 [PMID: 16646809]
  36. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14674-9 [PMID: 11121068]
  37. FEMS Microbiol Rev. 2010 Jul;34(4):588-605 [PMID: 20337720]
  38. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5154-9 [PMID: 20133735]
  39. Mol Microbiol. 2002 Oct;46(2):331-47 [PMID: 12406212]
  40. Annu Rev Microbiol. 2007;61:349-77 [PMID: 17506680]
  41. Nat Methods. 2007 Feb;4(2):147-52 [PMID: 17179933]
  42. Microb Pathog. 2013 Dec;65:89-96 [PMID: 24184341]
  43. J Mol Microbiol Biotechnol. 2009;17(1):20-9 [PMID: 18824837]
  44. BMC Genomics. 2013 Oct 17;14:710 [PMID: 24134787]
  45. J Microbiol Biotechnol. 2007 Feb;17(2):187-94 [PMID: 18051748]
  46. Nat Biotechnol. 2011 Jan;29(1):24-6 [PMID: 21221095]
  47. Mol Microbiol. 2008 Feb;67(4):861-80 [PMID: 18179599]
  48. J Exp Med. 2003 Sep 1;198(5):705-13 [PMID: 12953092]
  49. Genome Biol. 2009;10(3):R25 [PMID: 19261174]
  50. Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6554-9 [PMID: 23576728]
  51. J Proteome Res. 2012 Jul 6;11(7):3888-96 [PMID: 22650367]
  52. BMC Syst Biol. 2007 Jun 08;1:26 [PMID: 17555602]
  53. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):E4256-65 [PMID: 24145454]
  54. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1096-101 [PMID: 24395772]
  55. Mol Microbiol. 2005 Oct;58(2):580-95 [PMID: 16194241]
  56. Appl Microbiol Biotechnol. 2011 Feb;89(4):1149-59 [PMID: 21229241]
  57. Microbiology. 2009 Apr;155(Pt 4):1332-9 [PMID: 19332834]
  58. EMBO J. 2014 Aug 18;33(16):1802-14 [PMID: 24986881]
  59. BMC Genomics. 2013 Jul 02;14:436 [PMID: 23819599]
  60. Microb Pathog. 2009 Apr;46(4):185-93 [PMID: 19272305]
  61. Nature. 2013 Jul 11;499(7457):178-83 [PMID: 23823726]
  62. Tuberculosis (Edinb). 2013 Mar;93(2):198-206 [PMID: 23352854]
  63. PLoS One. 2010 Oct 26;5(10):e13356 [PMID: 21048946]
  64. BMC Microbiol. 2010 May 11;10:138 [PMID: 20459763]

Grants

  1. MR/J006874/1/Medical Research Council
  2. BB/G020434/1/Biotechnology and Biological Sciences Research Council

MeSH Term

Ammonium Compounds
Aspartic Acid
Bacterial Proteins
Binding Sites
Cell Wall
Chromatin Immunoprecipitation
Gene Expression Profiling
Gene Expression Regulation, Bacterial
Metabolic Networks and Pathways
Mycobacterium tuberculosis
Nitrogen
Protein Binding
Response Elements
Stress, Physiological

Chemicals

Ammonium Compounds
Bacterial Proteins
Aspartic Acid
Nitrogen
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 9

Word Cloud

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