These authors contributed equally to this work.
Mannan core branching of lipo(arabino)mannan is required for mycobacterial virulence in the context of innate immunity
Version of Record online: 22 AUG 2013
© 2013 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 15, Issue 12, pages 2093–2108, December 2013
How to Cite
Stoop, E. J. M., Mishra, A. K., Driessen, N. N., van Stempvoort, G., Bouchier, P., Verboom, T., van Leeuwen, L. M., Sparrius, M., Raadsen, S. A., van Zon, M., van der Wel, N. N., Besra, G. S., Geurtsen, J., Bitter, W., Appelmelk, B. J. and van der Sar, A. M. (2013), Mannan core branching of lipo(arabino)mannan is required for mycobacterial virulence in the context of innate immunity. Cellular Microbiology, 15: 2093–2108. doi: 10.1111/cmi.12175
The copyright line for this article was changed on 18 October 2014 after original online publication.
- Issue online: 15 NOV 2013
- Version of Record online: 22 AUG 2013
- Accepted manuscript online: 31 JUL 2013 04:07AM EST
- Manuscript Accepted: 17 JUL 2013
- Manuscript Revised: 3 JUL 2013
- Manuscript Received: 25 FEB 2013
- Smart Mix Program of the Netherlands Ministry of Economic Affairs
- Netherlands Ministry of Education, Culture and Science
- Royal Society Wolfson Research Merit Award
- Medical Research Council
- Wellcome Trust. Grant Number: 081569/Z/06/Z
- Netherlands Organization for Scientific Research (NOW). Grant Number: 016.101.001
The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, remains an important worldwide health threat. Although TB is one of the oldest infectious diseases of man, a detailed understanding of the mycobacterial mechanisms underlying pathogenesis remains elusive. Here, we studied the role of the α(12) mannosyltransferase MptC in mycobacterial virulence, using the Mycobacterium marinum zebrafish infection model. Like its M. tuberculosis orthologue, disruption of M. marinum mptC (mmar_3225) results in defective elongation of mannose caps of lipoarabinomannan (LAM) and absence of α(12)mannose branches on the lipomannan (LM) and LAM mannan core, as determined by biochemical analysis (NMR and GC-MS) and immunoblotting. We found that the M. marinum mptC mutant is strongly attenuated in embryonic zebrafish, which rely solely on innate immunity, whereas minor virulence defects were observed in adult zebrafish. Strikingly, complementation with the Mycobacterium smegmatis mptC orthologue, which restored mannan core branching but not cap elongation, was sufficient to fully complement the virulence defect of the mptC mutant in embryos. Altogether our data demonstrate that not LAM capping, but mannan core branching of LM/LAM plays an important role in mycobacterial pathogenesis in the context of innate immunity.