Metabolism was once relegated to the supply of energy and biosynthetic precursors, but it has now become clear that it is a specific mediator of nearly all physiological processes. In the context of microbial pathogenesis, metabolism has expanded outside its canonical role in bacterial replication. Among human pathogens, this expansion has emerged perhaps nowhere more visibly than for Mycobacterium tuberculosis, the causative agent of tuberculosis. Unlike most pathogens, M. tuberculosis has evolved within humans, which are both host and reservoir. This makes unrestrained replication and perpetual quiescence equally incompatible strategies for survival as a species. In this Review, we summarize recent work that illustrates the diversity of metabolic functions that not only enable M. tuberculosis to establish and maintain a state of chronic infection within the host but also facilitate its survival in the face of drug pressure and, ultimately, completion of its life cycle.
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This work was supported by grants R01AI063446 (National Institute of Allergy and Infectious Diseases (NIAID)) and U19AI111143 (Tri-Institutional TB Research Unit, part of the NIAID Tuberculosis Research Units Network).
Nature Reviews Microbiology thanks Johnjoe McFadden, Olivier Neyrolles and the other anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The necrotic death of cells in the centre of a granuloma, resulting in an acellular mass that resembles a soft, crumbly cheese.
- Tricarboxylic acid cycle
(TCA cycle). A biochemical energy-generating pathway for the final steps of the oxidation of carbohydrates and fatty acids.
- Glyoxylate shunt
An anaplerotic pathway that converts isocitrate into malate and succinate, bypassing the two decarboxylation steps of the tricarboxylic acid cycle.
The process of replenishing metabolite pools.
Involving the process of extracting metabolites for biosynthetic reactions.
The accumulation of high concentrations of the ketones acetoacetate and β-hydroxybutyrate.
A compound that readily reacts with an unsaturated hydrocarbon (diene).
The aggregation of mycobacteria in a structure that resembles cords. This is due to the glycolipid trehalose dimycolate, also called cord factor.
The physical property of the mycolic acid-containing mycobacterial cell envelope that is responsible for resistance to decolorization by acid and ethanol.
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Ehrt, S., Schnappinger, D. & Rhee, K.Y. Metabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis. Nat Rev Microbiol 16, 496–507 (2018). https://doi.org/10.1038/s41579-018-0013-4
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