Peptidoglycans

Glycobiology Analysis Manual, 2nd Edition

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Peptidoglycans

Structure

The basic structure of peptidoglycan (PGN) contains a carbohydrate backbone of alternating units of N-acetylglucosamine (GlcNAc) and Nacetylmuramic acid, with the N-acetylmuramic acid residues cross-linked to peptides. Peptidoglycan provides rigidity to the cell wall; the cell walls of Gram-positive bacteria may contain up to 40 layers of peptidoglycan, conferring significant mechanical strength.1

Structurally, bacteria resemble primitive plants in that the cellular contents are surrounded by an inner peptidoglycan cell wall in addition to an inner plasma membrane and, in Gram-negative bacteria, an outer lipid bilayer (see Figure 1). In Gram-negative bacteria, peptidoglycans make up about 10% of the cell wall dry weight; while in Gram-positive bacteria the thicker peptidoglycan layer contains about 20% of the cell wall dry weight. Although the peptidoglycan is responsible for the mechanical strength and shape of bacterial cells, it has sufficient plasticity and dynamic turnover to allow cell growth and division.

The basic structure of bacterial peptidoglycan and the cell wall structures of Gram-positive and Gram-negative bacteria

Figure 1. The basic structure of bacterial peptidoglycan and the cell wall structures of Gram-positive and Gram-negative bacteria.

Biosynthesis and Degradation

The peptidoglycan biosynthetic pathway begins in the cytoplasm with the synthesis of a muramyl peptapeptide precursor containing a terminal D-Ala-D-Ala. L-Alanine is converted to D-alanine by racemase, with subsequent assembly of D-alanyl-D-alanine by D-Ala-D-Ala ligase. In the cytoplasm, the muramyl pentapeptide precursor is anchored via a water-soluble UDP-glucosamine moiety. In the second phase of peptidoglycan construction, the muramyl pentapeptide N-acetylglucosamine is transferred to a C55 undecaprenyl phosphate with the release of UMP to form a Lipid I intermediate. An additional glycosylation step completes the peptidoglycan unit, which is then transported via its C55 lipid tail to the external periplasmic surface of the membrane, where the peptidyglycan unit becomes integrated into the cell wall matrix. Several transpeptidases and transglycosylases connect the newly formed peptidoglycan structures to the cell wall peptidoglycan matrix.

Inhibitors of peptidoglycan biosynthesis act as antibiotics in that they lead sequentially to the loss of peptidoglycan, loss of cell wall integrity, and lysis. Peptidoglycan degradation is catalyzed by glycosidases, peptidases, and amidases, including lysing enzymes such as lysozyme, that are commonly used for degrading cell walls.

Specific antibacterial compounds that contain a β-lactam structure, such as penicillin, interfere with the synthesis of the cell wall, weakening the peptidoglycan scaffold within the bacterial wall so the structural integrity eventually fails. Since mammalian cells have a plasma membrane but lack the peptidoglycan wall structure, this class of antibacterials selectively targets bacteria with no significant negative effect on the cells of the mammalian host. The specificity of β-lactam antibacterials is due to their structural similarity to the D-alanyl-D-alanine group, allowing them to compete for the binding sites of transpeptidases and prevent the assembly of peptidoglycan layers in both Gram-positive and Gram-negative bacteria.

Functions

The primary immune recognition is based on structures common among invading pathogens. Surface molecules, such as lipopolysaccharide (LPS), peptidoglycans, and peptidoglycan recognition protein (PGRP), are known to elicit immune reactions ranging from cytokine release to fever.2‑4 Peptidoglycans activate the Toll-like receptor 2 (TLR2), that is present in mammalian cells, and they can be used for the stimulation of lymphocytes. Peptidoglycans also function as antagonists of Poly(I:C).5 Peptidoglycans may be used to estimate the activity of lysing enzymes such as lyticase.6

Materials

     

References

L J Wheat, B J Wilkinson, R B Kohler, A C White
Journal of Infectious Diseases 1983-01-01
Levels of antibodies to peptidoglycan were measured by solid-phase radioimmunoassay in 76 patients with Staphylococcus aureus infections and 44 patients with infections caused by other bacteria. Levels of IgM antibodies to peptidoglycan were elevated in 24% of the patients with endocarditis or complicated bacteremia caused by S....Read More
4. Doyle R.J., Dziarski R., in Molecular Medical Microbiology (Susmsman M., ed.) pp. 137‑153, Academic Press (2001).
L Alexopoulou, A C Holt, R Medzhitov, R A Flavell
Nature 2001-10-18
Toll-like receptors (TLRs) are a family of innate immune-recognition receptors that recognize molecular patterns associated with microbial pathogens, and induce antimicrobial immune responses. Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point ...Read More
R Zhou, S Chen, P Recsei
Analytical Biochemistry 1988-05-15
We describe a method for determination of lysostaphin activity using Remazol Brilliant Blue R (RBB)-dyed staphylococcal cells or RBB-dyed staphylococcal peptidoglycan as substrate. The dyed substrates are easy to prepare and are stable for at least 6 months. Soluble hydrolytic products released by lysostaphin are measured spectr...Read More
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