in monocytes and macrophages, epithelial intestinal cells, paneth cells, dendritic cells, osteoblasts, keratinocytes and other epithelial cell types. as cytosolic sensors, nod1 and nod2 must either detect bacteria that enter the cytosol, or peptidoglycan must be degraded to generate fragments that must be transported into the cytosol for these sensors to function. recently, it was demonstrated that nlrp3 is activated by peptidoglycan, through a mechanism that is independent of nod1 and nod2. in macrophages, n-acetylglucosamine generated by peptidoglycan degradation was found to inhibit hexokinase activity and induce its release from the mitochondrial membrane. it promotes nlrp3 inflammasome activation through a mechanism triggered by increased mitochondrial membrane permeability. nlrp1 is also considered as a cytoplasmic sensor of peptidoglycan. it can sense mdp and promote il-1 secretion through binding nod2. c-type lectin receptors (clrs) c-type lectins are a diverse superfamily of mainly ca2+-dependent proteins that bind a variety of carbohydrates (including the glycan skeleton of peptidoglycan), and function as innate immune receptors. clr proteins that bind to peptidoglycan include mbl (mannose binding lectin), ficolins, reg3a (regeneration gene family protein 3a) and ptclec1. in mammals, they initiate the lectin-pathway of the complement cascade. toll-like receptors the role of tlrs in direct recognition of peptidoglycan is controversial. in some studies, has been reported that peptidoglycan is sensed by tlr2. but this tlr2-inducing activity could be due to cell wall lipoproteins and lipoteichoic acids that commonly co-purify with peptidoglycan. also variation in peptidoglycan structure in bacteria from species to species may contribute to the differing results on this topic. as vaccine or adjuvant peptidoglycan is immunologically active, which can stimulate immune cells to increase the expression of cytokines and enhance antibody-dependent specific response when combined with vaccine or as adjuvant alone. mdp, which is the basic unit of peptidoglycan, was initially used as the active component of freund's adjuvant. peptidoglycan from staphylococcus aureus was used as a vaccine to protect mice, showing that after vaccine injection for 40 weeks, the mice survived from s. aureus challenge at an increased lethal dose. inhibition and degradation some antibacterial drugs such as penicillin interfere with the production of peptidoglycan by binding to bacterial enzymes known as penicillin-binding proteins or dd-transpeptidases. penicillin-binding proteins form the bonds between oligopeptide crosslinks in peptidoglycan. for a bacterial cell to reproduce through binary fission, more than a million peptidoglycan subunits (nam-nag+oligopeptide) must be attached to existing subunits. mutations in genes coding for transpeptidases that lead to reduced interactions with an antibiotic are a significant source of emerging antibiotic resistance. since peptidoglycan is also lacking in l-form bacteria and in mycoplasmas, both are resistant against penicillin. other steps of peptidoglycan synthesis can also be targeted. the topical antibiotic bacitracin targets the utilization of c55-isoprenyl pyrophosphate. lantibiotics, which includes the food preservative nisin, attack lipid ii. lysozyme, which is found in tears and constitutes part of the body's innate immune system exerts its antibacterial effect by breaking the β-(1,4)-glycosidic bonds in peptidoglycan (see above). lysozyme is more effective in acting against gram-positive bacteria, in which the peptidoglycan cell wall is exposed, than against gram-negative bacteria, which have an outer layer of lps covering the peptidoglycan layer. several bacterial peptidoglycan modifications can result in resistance to degradation by lysozyme. susceptibility of bacteria to degradation is also considerably affected by exposure to antibiotics. exposed bacteria synthesize peptidoglycan that contains shorter sugar chains that are poorly crosslinked and this peptidoglycan is then more easily degraded by lysozyme.