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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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.
The authors declare no competing financial interests.
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Eoh, H., Wang, Z., Layre, E. et al. Metabolic anticipation in Mycobacterium tuberculosis. Nat Microbiol 2, 17084 (2017). https://doi.org/10.1038/nmicrobiol.2017.84
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