Mycobacterial Lipidomics and Cellular Interactions

Mycobacterial lipidomics has transformed our understanding of the complex interplay between mycobacterial cell envelopes and host cells. The distinctive repertoire of lipids produced by Mycobacterium species—including mycolic acids, sulfoglycolipids and terpene nucleosides—underpins both pathogen survival and host immune modulation. Detailed lipid profiles reveal how cell-wall components contribute to permeability barriers, pathogen persistence and evasion of host defences. Advances in mass spectrometry and chromatographic separation now permit high-resolution mapping of lipid classes, collision cross sections and dynamic remodelling events. These insights elucidate mechanisms of phagosome arrest, lysosomal failure, membrane reorganisation and nutrient acquisition in infected macrophages. Integrating lipidomic data with functional assays has highlighted novel biomarkers of infection and unveiled therapeutic targets for host-directed interventions. Collectively, this field bridges basic biochemical characterisation with cellular immunology, offering a holistic view of mycobacterial pathogenesis and avenues for diagnostic and drug-development strategies.

Research from Nature Portfolio

High-precision ion mobility-mass spectrometry has been applied to catalogue over 200 distinct collision cross sections of mycolic acids across pathogenic and non-pathogenic Mycobacterium species. By correlating acyl-tail length and specific modifications with gas-phase mobility signatures, researchers have created an open database that enables rapid species differentiation and comparative studies of cell-wall architecture. This resource supports investigations into lineage-specific lipid phenotypes and informs drug-target validation efforts against lipid biosynthetic enzymes. In parallel, a combined biophysical and cell-biology approach has illuminated how a virulent sulfoglycolipid reconfigures host plasma membranes. This glycolipid alters membrane order, fluidity and stiffness, disrupts cytoskeletal interactions and dampens membrane-associated autophagy signalling. The study elucidates lipid-driven mechanisms of immune evasion and identifies membrane biophysical parameters as potential therapeutic intervention points.

Mycobacterial Lipidomics and Cellular Interactions publication trend

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

Technical terms

Lipidomics: Global characterisation of lipid species within a biological system, typically by mass spectrometry.

Mycolic acids: Long-chain α-alkyl, β-hydroxy fatty acids unique to mycobacterial cell envelopes.

Ion mobility-mass spectrometry: Technique that separates ions by collision cross section before mass analysis to resolve structural isomers.

Terpene nucleosides: Hybrid molecules combining isoprenoid and nucleoside units, implicated in host–pathogen signalling.

Foamy macrophages: Lipid-rich immune cells that harbour intracellular pathogens and serve as nutrient reservoirs.

Sulfoglycolipid-1: Sulphated trehalose-derived glycolipid that remodels host membrane biophysics during infection.

References

1. Ion mobility mass spectrometry for the study of mycobacterial mycolic acids. Scientific Reports (2023).
2. Dynamic Remodeling of the Host Cell Membrane by Virulent Mycobacterial Sulfoglycolipid-1. Scientific Reports (2019).
3. A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages. Journal of Clinical Investigation (2023).
4. Mycobacteria that cause tuberculosis have retained ancestrally acquired genes for the biosynthesis of chemically diverse terpene nucleosides. PLOS Biology (2024).