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Lipoarabinomannan biosynthesis in Corynebacterineae: the interplay of two α(1→2)-mannopyranosyltransferases MptC and MptD in mannan branching.
- Source :
-
Molecular microbiology [Mol Microbiol] 2011 Jun; Vol. 80 (5), pp. 1241-59. Date of Electronic Publication: 2011 Apr 04. - Publication Year :
- 2011
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Abstract
- 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.<br /> (© 2011 Blackwell Publishing Ltd.)
- Subjects :
- Bacterial Proteins genetics
Biosynthetic Pathways
Corynebacterium glutamicum chemistry
Corynebacterium glutamicum enzymology
Corynebacterium glutamicum genetics
Lipopolysaccharides chemistry
Molecular Structure
Phosphoenolpyruvate Sugar Phosphotransferase System genetics
Bacterial Proteins metabolism
Corynebacterium glutamicum metabolism
Lipopolysaccharides biosynthesis
Mannans metabolism
Phosphoenolpyruvate Sugar Phosphotransferase System metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2958
- Volume :
- 80
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 21435038
- Full Text :
- https://doi.org/10.1111/j.1365-2958.2011.07640.x