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Lipoarabinomannan of Mycobacterium tuberculosis. Capping with mannosyl residues in some strains
D Chatterjee1, K Lowell, B Rivoire
1Department of Microbiology, Colorado State University, Fort Collins 80523.
Abstract:
Previously we had demonstrated that the termini of the arabinan component of mycobacterial cell wall arabinogalactan, the site of mycolic acid location, consists mostly of clusters of a pentaarabinofuranoside, [beta-D-Araf-(1----2)-alpha-D-Araf-(1----]2----(3 and 5)-alpha-D-Araf. Subsequently, the same arrangement was shown to dominate the non-reducing ends of lipoarabinomannan (LAM), a key component in the interaction of mycobacteria with host cell. Accordingly, we had proposed that mycobacteria universally elaborate the same Araf-containing motifs in two settings for different pathophysiological purposes. However, we now report that the termini of LAM from the virulent, Erdman, strain of Mycobacterium tuberculosis, unlike those from the attenuated H37Ra strain, are extensively capped with mannosyl (Manp) residues, either a single alpha-D-Manp, a dimannoside (alpha-D-Manp-(1----2)-alpha-D-Manp), or a trimannoside (alpha-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp ). The use of monoclonal antibodies demonstrates a clear difference in the antigenicity of the basic and mannose-capped LAM. The possibility that these structures are a factor in the virulence of some strains of M. tuberculosis and represent an example of carbohydrate mimicry in mycobacterial infections is discussed.
Insights
Mycobacterium tuberculosis strains differ in their lipoarabinomannan (LAM) structures. Virulent strains possess mannose-capped LAM, unlike attenuated strains, suggesting a role in virulence and host interaction.
Area of Science:
- Microbiology
- Immunology
- Glycobiology
Background:
- Mycobacterial cell walls contain arabinogalactan and lipoarabinomannan (LAM).
- Previously, a conserved arabinofuranoside motif was identified at the termini of these structures.
- This motif was proposed to be universally elaborated by mycobacteria for various pathophysiological roles.
Purpose of the Study:
- To investigate differences in the terminal structures of LAM from virulent and attenuated Mycobacterium tuberculosis strains.
- To explore the potential implications of these structural variations in mycobacterial virulence and host interactions.
Main Methods:
- Analysis of lipoarabinomannan (LAM) terminal structures from Mycobacterium tuberculosis strains (Erdman and H37Ra).
- Characterization of mannosyl (Manp) residue capping on LAM using monoclonal antibodies.
Main Results:
- LAM from the virulent Erdman strain of M. tuberculosis is extensively capped with mannosyl residues.
- LAM from the attenuated H37Ra strain lacks this mannose capping.
- Monoclonal antibodies revealed distinct antigenicity between mannose-capped and basic LAM.
Conclusions:
- Significant structural differences exist in LAM termini between virulent and attenuated M. tuberculosis strains.
- Mannose-capped LAM structures in virulent strains may contribute to virulence.
- These structures could represent a mechanism of carbohydrate mimicry in mycobacterial infections.