Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 209, Issue 7, Pages 1045-1054Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit622
Keywords
tuberculosis; NOD2; N-glycolyl MDP; N-acetyl muramic acid hydroxylase; NamH
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Funding
- CIHR and a European Research Council [MOP-97813, MOP-115133]
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Mycobacteria produce an unusual, glycolylated form of muramyl dipeptide (MDP) that is more potent and efficacious at inducing NOD2-mediated host responses. We tested the importance of this modified form of MDP in Mycobacterium tuberculosis by disrupting the gene, namH, responsible for this modification. In vitro, the namH mutant did not produce N-glycolylated muropeptides, but there was no alteration in colony morphology, growth kinetics, cellular morphology, or mycolic acid profile. Ex vivo, the namH mutant survived and replicated normally in murine and human macrophages, yet induced diminished production of tumor necrosis factor alpha. In vivo, namH disruption did not affect the bacterial burden during infection of C57BL/6 mice or cellular recruitment to the lungs but modestly prolonged survival after infection in Rag1(-/-) mice. These results indicate that the modified MDP is an important contributor to the unusual immunogenicity of mycobacteria but has a limited role in the pathogenesis of M. tuberculosis infection.
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