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Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). Attached to the N-acetylmuramic acid is an oligopeptide chain made of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer. Peptidoglycan serves a structural role in the bacterial cell wall, giving structural strength, as well as counteracting the osmotic pressure of the cytoplasm. This repetitive linking results in a dense peptidoglycan layer which is critical for maintaining cell form and withstanding high osmotic pressures, and it is regularly replaced by peptidoglycan production. Peptidoglycan hydrolysis and synthesis are two processes that must occur in order for cells to grow and multiply, a technique carried out in three stages: clipping of current material, insertion of new material, and re-crosslinking of existing material to new material.
The peptidoglycan layer is substantially thicker in gram-positive bacteria (20 to 80 nanometers) than in gram-negative bacteria (7 to 8 nanometers). Depending on pH growth conditions, the peptidoglycan forms around 40 to 90% of the cell wall's dry matter of gram-positive bacteria but only around 10% of gram-negative strains. Thus, presence of high levels of peptidoglycan is the primary determinant of the characterisation of bacteria as gram-positive. In gram-positive strains, it is important in attachment roles and serotyping purposes. (1996). 9780963117212, Univ of Texas Medical Branch. ISBN 9780963117212 For both gram-positive and gram-negative bacteria, particles of approximately 2 nm can pass through the peptidoglycan.
It is difficult to tell whether an organism is gram-positive or gram-negative using a microscope; , created by Hans Christian Gram in 1884, is required. The bacteria are stained with the dyes crystal violet and safranin. Gram positive cells are purple after staining, while Gram negative cells stain pink.
By enclosing the inner membrane, the peptidoglycan layer protects the cell from lysis caused by the Turgor pressure pressure of the cell. When the cell wall grows, it retains its shape throughout its life, so a rod shape will remain a rod shape, and a spherical shape will remain a spherical shape for life. This happens because the freshly added septal material of synthesis transforms into a hemispherical wall for the offspring cells.
between in different linear amino sugar chains occurs with the help of the enzyme DD-transpeptidase and results in a 3-dimensional structure that is strong and rigid. The specific amino acid sequence and molecular structure vary with the bacterial species. (2025). 9780838585290, McGraw Hill. ISBN 9780838585290
The different peptidoglycan types of bacterial cell walls and their taxonomic implications have been described. Archaea (domain Archaea) do not contain peptidoglycan (murein). Some Archaea contain pseudopeptidoglycan (pseudomurein, see below).
File:Gram-positive cellwall-schematic.png|Gram-positive cell wall
File:PBP catalysis.svg|Penicillin binding protein forming cross-links in newly formed bacterial cell wall.
In the course of early evolution, the successive development of boundaries (membranes, walls) protecting first structures of life against their environment must have been essential for the formation of the first cells (Cellularization).
The invention of rigid peptidoglycan (murein) cell walls in bacteria (domain Bacteria) was probably the prerequisite for their survival, extensive radiation and colonisation of virtually all habitats of the geosphere and hydrosphere. (1994). 9780231080880, Columbia U.P.. ISBN 9780231080880 (1998). 9780203484203, Taylor and Francis Ltd.. ISBN 9780203484203
Each of these reactions requires the energy source ATP. This is all referred to as Stage one.
Stage two occurs in the cytoplasmic membrane. It is in the membrane where a lipid carrier called bactoprenol carries peptidoglycan precursors through the cell membrane.
Peptidoglycans can be degraded by several enzymes (lysozyme, glucosaminidase, endopeptidase...), producing immunostimulatory fragments (sometimes called muropeptides) that are critical for mediating host-pathogen interactions. These include MDP (muramyl dipeptide), NAG (N-acetylglucosamine) or iE-DAP (γ-d-glutamyl-meso-diaminopimelic acid).
Peptidoglycan from Gut microbiota (both pathogens and commensals) crosses the intestinal barrier even under physiological conditions. Mechanisms through which peptidoglycan or its fragments enter the host cells can be direct (carrier-independent) or indirect (carrier-dependent), and they are either bacteria-mediated (secretion systems, membrane vesicles) or host cell-mediated (receptor-mediated, peptide transporters). Bacterial secretion systems are protein complexes used for the delivery of virulence factors across the bacterial cell envelope to the exterior environment. Intracellular bacterial pathogens invade eukaryotic cells (which may lead to the formation of and/or autophagy activation), or bacteria may be engulfed by (, , ...). The bacteria-containing phagosome may then fuse with and , leading to degradation of bacteria and generation of polymeric peptidoglycan fragments and muropeptides.
Each of the mammalian PGLYRPs display unique tissue expression patterns. PGLYRP-1 is mainly expressed in the granules of and . PGLYRP-3 and 4 are expressed by several tissues such as skin, sweat glands, eyes or the intestinal tract. PGLYRP-1, 3 and 4 form disulphide-linked homodimers and heterodimers essential for their bactericidal activity. Their binding to bacterial cell wall peptidoglycans can induce bacterial cell death by interaction with various bacterial transcriptional regulatory proteins. PGLYRPs are likely to assist in bacterial killing by cooperating with other PRRs to enhance recognition of bacteria by phagocytes.
PGLYRP-2 is primarily expressed by the liver and secreted into the circulation. Also, its expression can be induced in skin , oral and intestinal Epithelium cells. In contrast with the other PGLYRPs, PGLYRP-2 has no direct bactericidal activity. It possesses peptidoglycan amidase activity, it hydrolyses the lactyl-amide bond between the MurNAc and the first amino acid of the stem peptide of peptidoglycan. It is proposed, that the function of PGLYRP-2 is to prevent over-activation of the immune system and inflammation-induced tissue damage in response to NOD2 ligands (see below), as these muropeptides can no longer be recognized by NOD2 upon separation of the peptide component from MurNAc. Growing evidence suggests that peptidoglycan recognition protein family members play a dominant role in the tolerance of intestinal epithelial cells toward the commensal microbiota. It has been demonstrated that expression of PGLYRP-2 and 4 can influence the composition of the intestinal microbiota.
Recently, it has been discovered, that PGLYRPs (and also NOD-like receptors and peptidoglycan transporters) are highly expressed in the developing mouse brain. PGLYRP-2 and is highly expressed in of several brain regions including the prefrontal cortex, hippocampus, and cerebellum, thus indicating potential direct effects of peptidoglycan on neurons. PGLYRP-2 is highly expressed also in the cerebral cortex of young children, but not in most adult cortical tissues. PGLYRP-1 is also expressed in the brain and continues to be expressed into adulthood.
NOD1 is expressed by diverse cell types, including myeloid phagocytes, epithelial cells and neurons. NOD2 is expressed in monocytes and macrophages, epithelial intestinal cells, , , , keratinocytes and other epithelial cell types. As 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 Mitochondrion 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.
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 . Exposed bacteria synthesize peptidoglycan that contains shorter sugar chains that are poorly crosslinked and this peptidoglycan is then more easily degraded by lysozyme.
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