Bacteria modify PG to increase resistance to lysozyme, and some modifications can affect downstream innate detection.

To disrupt efficient lysozyme binding to PG (A), bacteria modify their PG via N-deacetylation of NAG (B), O-acetylation of NAM (C), and N-glycolylation of NAM (D). Bacteria that N-deacetylate NAM (E), add WTAs to NAM (F), highly crosslink their PG (G), or amidate D-glutamic acid (H) are also more resistant to lysozyme. NAM on PG fragments that are released by lysozyme are in a reduced form and can activate the pattern recognition receptors NOD1 (I) and NOD2 (J). In contrast, PG released by bacterial lytic transglycosylases occurs with the formation of a 1,6-anhydrobond on the NAM residue, which can prevent NOD2 detection (K). N-deacetylation of NAM and N-glycolylation of NAM can decrease and increase NOD2-PG detection, respectively, whereas O-acetylation of NAM does not affect NOD2-PG detection. Abbreviations: NAG, N-acetylglucosamine; NAM, N-acetylmuramic acid; PG, peptidoglycan; WTAs, wall teichoic acids.