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Lipoarabinomannan biosynthesis in Corynebacterineae: the interplay of two α(1→2)-mannopyranosyltransferases MptC and MptD in mannan branching.
Mol Microbiol. 2011 Jun; 80(5):1241-59
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26 Jul 2011
New Finding, Technical Advance
DOI: 10.3410/f.11993964.13128055
In this interesting article the authors provide new insights into the biosynthesis of lipoarabinomannan (LAM), a component of the complex cell wall of the Corynebacterineae.
They use bacterial mutants, chemical analysis and enzymatic data to demonstrate that Corynebacterium glutamicum mannopyranosyltransferase (Mpt)C, its Mycobacterium tuberculosis (Mtb) homologue, Rv2181, and C. glutamicum MptD function as alpha(1-2)-mannopyranosyltransferases. These enzymes are required for complete mannose branching in the important cell wall lipoglycans lipomannan (LM) and LAM. Although the role of these molecules is poorly defined in Corynebacterium, they are extremely important in Mtb pathogenesis. This study also describes a novel, blocked nonasaccharide acceptor that allows for the evaluation of distinct alpha(1-2)-mannopyranosyletransferases and has the potential to be used for further evaluation of these types of enzymes in Corynebacterineae. By expanding the knowledge of the enzymes that contribute to the synthesis of the complex cell wall and by providing a new technique to study these enzymes, the authors not only contribute to a better understanding of the biology of the bacteria but also highlight possible targets for novel chemotherapies.
Disclosures
None declared
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Ehrt S and Small J: F1000Prime Recommendation of [Mishra AK et al., Mol Microbiol 2011, 80(5):1241-59]. In F1000Prime, 26 Jul 2011; DOI: 10.3410/f.11993964.13128055. F1000Prime.com/11993964#eval13128055
F1000Prime Recommendations, Dissents and Comments for [Mishra AK et al., Mol Microbiol 2011, 80(5):1241-59]. In F1000Prime, 20 Jun 2013; F1000Prime.com/11993964
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Lipomannan (LM) and lipoarabinomannan (LAM) are key Corynebacterineae glycoconjugates that are integral components of the mycobacterial cell wall, and are potent immunomodulators during infection. LAM is a complex heteropolysaccharide synthesized by an array of essential glycosyltransferase family C (GT-C) members, which represent potential drug targets. Herein, we have identified and characterized two open reading frames from Corynebacterium glutamicum that encode for putative GT-Cs. Deletion of NCgl2100 and NCgl2097 in C. glutamicum demonstrated their role in the biosynthesis of the branching α(1→2)-Manp residues found in LM and LAM. In addition, utilizing a chemically defined nonasaccharide acceptor, azidoethyl 6-O-benzyl-α-D-mannopyranosyl-(1→6)-[α-D-mannopyranosyl-(1→6)](7) -D-mannopyranoside, and the glycosyl donor C(50) -polyprenol-phosphate-[(14) C]-mannose with membranes prepared from different C. glutamicum mutant strains, we have shown that both NCgl2100 and NCgl2097 encode for novel α(1→2)-mannopyranosyltransferases, which we have termed MptC and MptD respectively. Complementation studies and in vitro assays also identified Rv2181 as a homologue of Cg-MptC in Mycobacterium tuberculosis. Finally, we investigated the ability of LM and LAM from C. glutamicum, and C. glutamicumΔmptC and C. glutamicumΔmptD mutants, to activate Toll-like receptor 2. Overall, our study enhances our understanding of complex lipoglycan biosynthesis in Corynebacterineae and sheds further light on the structural and functional relationship of these classes of polysaccharides.
© 2011 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2011.07640.x
PMID: 21435038
