Abstract
Similar to other prokaryotes, mycobacteria decorate their major cell envelope glycans with minor covalent substituents whose biological significance remains largely unknown. We report on the discovery of a mycobacterial enzyme, named here SucT, that adds succinyl groups to the arabinan domains of both arabinogalactan (AG) and lipoarabinomannan (LAM). Disruption of the SucT-encoding gene in Mycobacterium smegmatis abolished AG and LAM succinylation and altered the hydrophobicity and rigidity of the cell envelope of the bacilli without significantly altering AG and LAM biosynthesis. The changes in the cell surface properties of the mutant were consistent with earlier reports of transposon mutants of the closely related species Mycobacterium marinum and Mycobacterium avium harboring insertions in the orthologous gene whose ability to microaggregate and form biofilms were altered. Our findings point to an important role of SucT-mediated AG and LAM succinylation in modulating the cell surface properties of mycobacteria.
Highlights
Similar to other prokaryotes, mycobacteria decorate their major cell envelope glycans with minor covalent substituents whose biological significance remains largely unknown
The finding of covalent substituents modifying the structures of two of the dominant heteropolysaccharides produced by all Mycobacterium species, arabinogalactan (AG)2 and lipoarabinomannan (LAM), suggests that mycobacteria have evolved similar strategies as other prokaryotes to promote their survival in different environments [12]
In Mycobacterium tuberculosis and a number of other slow- and fast-growing pathogenic mycobacteria (Mycobacterium avium, Mycobacterium kansasii, Mycobacterium bovis, Mycobacterium leprae, and Mycobacterium abscessus), the C2 position of a portion of the internal ␣-3,5–branched Araf residues of the arabinan domain of AG may be modified with galactosamine substituents, a motif not found in LAM [13] (Fig. 1)
Summary
Succinate groups were found to substitute the same positions of the arabinan domain as well as quantitatively minor ␣-1,5-Araf positions of AG from M. tuberculosis and Mycobacterium smegmatis [15], the internal ␣-3,5–branched Araf residues of the arabinan domain of LAM from M. bovis Bacillus CalmetteGuerin (BCG) [16], and possibly the same positions of LAM from M. leprae and M. tuberculosis [17,18,19,20,21]. Succinates were found to substitute the C3 position of linear ␣-1,5–Araf residues of LAM in M. kansasii [23] These observations are suggestive of the widespread distribution of succinate motifs in the AG and LAM of mycobacteria, even though their precise position on these glycans may be variable from species to species. Neither the enzyme(s) catalyzing the introduction of these motifs in the arabinan domain of AG, AM, and LAM nor the precise biological significance of polysaccharide succinylation in mycobacteria are currently known, even though an association was suggested between the charge of various LAM isoforms (in part driven by succinate content) and their ability to stimulate CD1b-restricted T cells [19, 21]. The possibility of generating mycobacterial mutants deficient in succinylation of cell envelope polysaccharides paves the way for studies aiming to determine the contribution of this discrete substituent to the physiology of slow- and fast-growing mycobacteria, their adaptation to the environment, and immunopathogenesis
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