Mannan core branching of lipo(arabino)mannan is required for mycobacterial virulence in the context of innate immunity

Esther J M Stoop, Arun K Mishra, Nicole N Driessen, Gunny van Stempvoort, Pascale Bouchier, Theo Verboom, Lisanne M van Leeuwen, Marion Sparrius, Susanne A Raadsen, Maaike van Zon, Nicole N van der Wel, Gurdyal S Besra, Jeroen Geurtsen, Wilbert Bitter, Ben J Appelmelk, Astrid M van der Sar

Research output: Contribution to journalArticlepeer-review

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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(1→2) 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(1→2) 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.
Original languageEnglish
Pages (from-to)2093–2108
JournalCellular Microbiology
Issue number12
Early online date22 Aug 2013
Publication statusPublished - 1 Dec 2013


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