Lipoarabinomannan of Mycobacterium tuberculosis. Capping with mannosyl residues in some strains.

D Chatterjee,K Lowell,B Rivoire,M.R Mcneil,P.J Brennan

doi:10.1016/s0021-9258(18)42686-5

D Chatterjee, K Lowell + Show 3 more

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https://doi.org/10.1016/s0021-9258(18)42686-5

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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.

Highlights

Wehad demonstrated that the termini of p-D-Araf-(l-Z)-(.-~-Araf-(l~5)-a-D-Araf or branched [pthearabinancomponentofmycobacterial cell wall D - A r a f - ( l - Z ) - a - ~ - A r a f - ( l - I ~ ~ ( 3 and 5)-a-D-Araf+
Manp-(1~2)-a-~-ManTph).e use of monoclonal anti- nan motifs are extensively substituted with either a single bodies demonstrates a clear difference in the antige- mannosyl residue, a dimannoside, or a trimannoside
The pos- implications of these observations in terms of the different sibility that these structures are a factor in the viru- orders of virulence/pathogenicity of different mycobacterial lence of some strains ofM. tuberculosis and represent strains are not obvious but do hint at elements of molecular an example of carbohydrate mimicry in mycobacterimalimicry on LAM, an important mycobacterial virulence facinfections is discussed

Summary

DISCUSSION

We had projected motifs A-D (Fig. 6), as they appearin the peptidoglycan-bound arabinogalactan of all mycobacteria, and the lipoarabinomannan of M. tuberculosis H37Ra, to molecular models of the holistic molecules [1,2]. Chains of glycoproteins from mammalian cell surfaces [23] This fact combined with the evidence of uncapped LAM in motif F was attached to a 5-linked a-Araf residue, while the certain mycobacteria may point to a form of carbohydrate structures of fragments/compounds 15 and 17 demonstrate “mimicry” in some strains of mycobacteria. The concept still abides that the induction of autoimmunity to mammalian hyaluronate by streptococcal infections with encapsulatedorganisms could be one mechanism for the induction of autoimmunity to tissue hyaluronate in man[27] It is clearly prematuretoattributethe phenomenon of carbohydrate mimicry to LAM from certain mycobacteria mine the degree of mannose capping of Man-LAMin M. based on presentevidence. Acknowledgments-We thank Marilyn Hein forpreparing the manuscript, Carol Marander and Carol Wade for graphics, and Dr Christopher Rithner for NMR spectroscopy

EXPERIMENTAL PROCEDURES

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