Mycobacterial Metabolism and Host Interactions

Mycobacteria such as Mycobacterium tuberculosis deploy sophisticated metabolic networks to sustain infection within diverse host niches. Lipid metabolism is central to pathogenesis, enabling exploitation of host fatty acids and cholesterol as carbon sources. Complex cell-wall lipid assemblies modulate host immunity, balancing pro-inflammatory and immunosuppressive signals. Intracellular survival hinges on detoxification systems that neutralise reactive nitrogen and oxygen species, heavy metals and antimicrobial peptides. Adaptation to in vivo stresses is orchestrated by transcriptional regulators that remodel metabolic pathways and transporter systems, often coupling nutrient uptake with evasion of host defences. Emerging evidence highlights reciprocal signalling between host-derived metabolites—such as aldehydes and transition metals—and mycobacterial enzymes, revealing vulnerabilities in protein homeostasis, redox balance and cofactor acquisition. Unravelling these interconnections offers new avenues for therapeutic intervention by targeting key enzymes and transporters critical for persistence.

Research from Nature Portfolio

Recent studies have characterised the Mce1 lipid uptake complex, revealing that a conserved membrane protein acts as a negative regulator by blocking assembly of the transporter subunits. Structural and biochemical analyses in a model mycobacterium demonstrate how fine-tuning of Mce1 function controls the import of fatty acids and may influence the balance between dormancy and active growth. By elucidating the architecture and regulation of this ATP-binding cassette-related system, this work provides a blueprint for disrupting lipid assimilation pathways in pathogenic species.

Mycobacterial Metabolism and Host Interactions publication trend

The graph below shows the total number of articles in mycobacterial metabolism and host interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Mce complex: Mammalian cell entry transporter system implicated in uptake of lipids by mycobacteria.

Proteasome: Multisubunit protease complex responsible for regulated protein degradation.

Cytochrome P450: Heme-containing monooxygenase enzyme family that catalyses diverse oxidation reactions.

ATP-binding cassette (ABC) transporter: Membrane protein complex that translocates substrates using ATP hydrolysis.

Aldehyde: Reactive organic compound with a terminal formyl group, implicated in host antimicrobial defence.

References

1. A conserved membrane protein negatively regulates Mce1 complexes in mycobacteria. Nature Communications (2023).
2. Aldehyde accumulation in Mycobacterium tuberculosis with defective proteasomal degradation results in copper sensitivity. mBio (2023).
3. Structure–Function Analysis of the Essential Mycobacterium tuberculosis P450 Drug Target, CYP121A1. International Journal of Molecular Sciences (2024).
4. Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis. eLife (2017).