Modification of the structure of peptidoglycan is a strategy to avoid detection by nucleotide-binding oligomerization domain protein 1

Infect Immun. 2007 Feb;75(2):706-13. doi: 10.1128/IAI.01597-06. Epub 2006 Dec 4.


Nucleotide-binding oligomerization domain (NOD) protein 1 (NOD1) and NOD2 are pathogen recognition receptors that sense breakdown products of peptidoglycan (PGN) (muropeptides). It is shown that a number of these muropeptides can induce tumor necrosis factor alpha (TNF-alpha) gene expression without significant TNF-alpha translation. This translation block is lifted when the muropeptides are coincubated with lipopolysaccharide (LPS), thereby accounting for an apparently synergistic effect of the muropeptides with LPS on TNF-alpha protein production. The compounds that induced synergistic effects were also able to activate NF-kappaB in a NOD1- or NOD2-dependent manner, implicating these proteins in synergistic TNF-alpha secretion. It was found that a diaminopimelic acid (DAP)-containing muramyl tetrapeptide could activate NF-kappaB in a NOD1-dependent manner, demonstrating that an exposed DAP is not essential for NOD1 sensing. The activity was lost when the alpha-carboxylic acid of iso-glutamic acid was modified as an amide. However, agonists of NOD2, such as muramyl dipeptide and lysine-containing muramyl tripeptides, were not affected by amidation of the alpha-carboxylic acid of iso-glutamic acid. Many pathogens modify the alpha-carboxylic acid of iso-glutamic acid of PGN, and thus it appears this is a strategy to avoid recognition by the host innate immune system. This type of immune evasion is in particular relevant for NOD1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Diaminopimelic Acid / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunity, Innate
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism
  • Molecular Structure
  • NF-kappa B / analysis
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Nod2 Signaling Adaptor Protein / metabolism
  • Peptidoglycan / chemistry*
  • Peptidoglycan / immunology*
  • Peptidoglycan / metabolism
  • Protein Binding
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics


  • Lipopolysaccharides
  • NF-kappa B
  • NOD1 protein, human
  • NOD2 protein, human
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Peptidoglycan
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Diaminopimelic Acid