Letter

Metabolic anticipation in Mycobacterium tuberculosis

  • Nature Microbiology 2, Article number: 17084 (2017)
  • doi:10.1038/nmicrobiol.2017.84
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Abstract

Humans serve as both host and reservoir for Mycobacterium tuberculosis, making tuberculosis a theoretically eradicable disease. How M. tuberculosis alternates between host-imposed quiescence and sporadic bouts of replication to complete its life cycle, however, remains unknown. Here, we identify a metabolic adaptation that is triggered upon entry into hypoxia-induced quiescence but facilitates subsequent cell cycle re-entry. Catabolic remodelling of the cell surface trehalose mycolates of M. tuberculosis specifically generates metabolic intermediates reserved for re-initiation of peptidoglycan biosynthesis. These adaptations reveal a metabolic network with the regulatory capacity to mount an anticipatory response.

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Acknowledgements

The authors thank G. Rehren and D. Schnappinger for advice in constructing knockout strains, C. Nathan, J. Vaubourgeix, S. Ehrt and S. Tavazoie for critical discussions and reading of the manuscript, S. Fischer for expert mass spectrometric support and the Bill and Melinda Gates Foundation Grand Challenges Exploration Program (OPP1068025) and National Institutes of Health Tri-I TBRU (U19-AI11143) for support.

Author information

Author notes

    • Hyungjin Eoh
    •  & Emilie Layre

    Present addresses: Keck School of Medicine, Department of Molecular Microbiology & Immunology, ZNI 537 1501 San Pablo, Los Angeles, California 90033, USA (H.E.); National Center for Scientific Research, Institute of Pharmacology & Structural Biology, 205 route de Narbonne BP64182, Toulouse 31077, France (E.L.).

Affiliations

  1. Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA

    • Hyungjin Eoh
    • , Zhe Wang
    • , Roxanne Morris
    •  & Kyu Y. Rhee
  2. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA

    • Emilie Layre
    •  & D. Branch Moody
  3. Department of Microbiology & Immunology, Weill Cornell Medical College, New York, New York 10065, USA

    • Poonam Rath
    •  & Kyu Y. Rhee

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Contributions

H.E. and Z.W. designed, conducted and analysed metabolomic profiling studies. E.L. and D.B.M. conducted and analysed lipidomic profiling studies. H.E. and P.R. conducted macrophage cytokine release assays. H.E., Z.W. and R.M. conducted antibiotic susceptibility assays. K.Y.R. initiated and directed this research.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Kyu Y. Rhee.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Figures 1–8.

Excel files

  1. 1.

    Supplementary Data 1

    All relevant source data related to metabolomic and lipidomic data shown in Figures 1–4 and Supplementary Figures 1–8.