Metabolic Interactions in Mycobacterium tuberculosis Infections

The host response to Mycobacterium tuberculosis involves profound metabolic reprogramming in both immune cells and the pathogen. Infection triggers a shift in macrophage energy pathways from mitochondrial oxidative phosphorylation to aerobic glycolysis, accompanied by depletion of NAD⁺ and altered redox balance. Concurrently, the bacterium induces lipid droplet formation in host cells and scavenges fatty acids to support its own lipid biosynthesis, dormancy and phenotypic drug tolerance. These intertwined metabolic adaptations underpin granuloma development, immune evasion and treatment challenges. Unravelling these pathways has revealed predictive biomarkers of treatment response and host-directed targets—such as enzymes governing glycolytic flux and lipid metabolism—to inform novel strategies against tuberculosis.

Research from Nature Portfolio

Recent studies have demonstrated that depletion of NAD⁺ by the pathogen impairs glycolytic flux in myeloid cells, weakening early immune recruitment and interferon-mediated protection. Restoration of NAD⁺ levels via nicotinamide supplementation enhances host defences and reduces bacterial burden in experimental models. Transcriptomic profiling and imaging of infected lung tissue have further revealed that immune cells adopt a Warburg-like metabolic profile in response to infection, upregulating key glycolytic enzymes while downregulating tricarboxylic acid cycle activity. Collectively, these findings underscore the central role of immunometabolic reprogramming in controlling infection and identify metabolic pathways as compelling targets for host-directed therapies.

Metabolic Interactions in Mycobacterium tuberculosis Infections publication trend

The graph below shows the total number of articles in metabolic interactions in mycobacterium tuberculosis infections across all publications each year (not limited to Nature Index journals).

Technical terms

Glycolysis: The enzymatic breakdown of glucose to pyruvate, yielding energy and metabolic intermediates.
Lipid droplet: Intracellular organelle storing neutral lipids, serving as a carbon reservoir that Mycobacterium tuberculosis exploits.
NAD⁺ homeostasis: The balance of nicotinamide adenine dinucleotide in its oxidised and reduced forms, essential for cellular redox reactions.
Warburg effect: The preference for aerobic glycolysis over oxidative phosphorylation, commonly observed in activated immune cells.
Immunometabolism: The study of how metabolic pathways influence the function and fate of immune cells.

References

1. NAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis. Nature Communications (2023).
2. Host and pathogen factors that influence variability of Mycobacterium tuberculosis lipid body content in sputum from patients with tuberculosis: an observational study. The Lancet Microbe (2024).
3. The fat is in the lysosome: how Mycobacterium tuberculosis tricks macrophages into storing lipids. Journal of Clinical Investigation (2023).
4. Host cell environments and antibiotic efficacy in tuberculosis. Trends in Microbiology (2023).
5. Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence. PLOS Pathogens (2008).
6. Mycobacterium tuberculosis Uses Host Triacylglycerol to Accumulate Lipid Droplets and Acquires a Dormancy-Like Phenotype in Lipid-Loaded Macrophages. PLOS Pathogens (2011).
7. Intracellular Mycobacterium tuberculosis Exploits Host-derived Fatty Acids to Limit Metabolic Stress*. Journal of Biological Chemistry (2013).
8. A Novel In Vitro Multiple-Stress Dormancy Model for Mycobacterium tuberculosis Generates a Lipid-Loaded, Drug-Tolerant, Dormant Pathogen. PLOS ONE (2009).
9. Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. Scientific Reports (2015).