Peptidoglycan is the rigid, but flexible, macromolecule that surrounds and protects individual bacterial cells. It supplies the foundation for bacterial cell walls, defines an organism's shape and anchors protein complexes and extracellular organelles to the cell surface, all while remaining porous enough to admit essential nutrients and large compounds. Peptidoglycan fragments trigger neighbouring microorganisms to grow or to modify their own walls, serve as maturation signals for vertebrate immune systems and may be used to manipulate the immune system for the benefit of pathogenic organisms. Because it is unique to bacteria, peptidoglycan is one of the most valuable targets to which antibiotics may be directed. Although the components of peptidoglycan are known and we have a basic understanding of its biosynthesis, there remains a great deal to learn about its three‐dimensional organisation, its biological properties and activities, and how it expands and divides during bacterial growth.

Key Concepts:

  • Peptidoglycan is the basic component of the bacterial cell wall, which is the protective structure that surrounds and protects most bacteria.

  • Peptidoglycan is composed of numerous glycan (sugar‐based) polymers that are covalently crosslinked to one another by short peptide side‐chains, creating a single bag‐like macromolecule called the sacculus.

  • Penicillin‐binding proteins are responsible for the final stages of peptidoglycan synthesis, but additional proteins modify peptidoglycan in numerous ways in different bacteria.

  • Because of its complexity, the exact three‐dimensional structure of peptidoglycan is not known, but it is thought to look like a net with pores 2–5 nm in diameter.

  • Large protein complexes and organelles are embedded in or are threaded through peptidoglycan, indicating that enzymes must degrade peptidoglycan in a limited way to create holes in which these structures may be assembled.

  • Bacteria can change the composition and perhaps the structure of their peptidoglycan, depending on growth conditions and in response to their environmental surroundings.

  • Peptidoglycan is constantly being broken down, recycled and renewed as bacteria grow and divide.

  • Bacteria use peptidoglycan fragments to signal or manipulate other microorganisms or even human and animal immune systems.

  • Because peptidoglycan is unique to bacteria, the enzymes that synthesise it are some of the most important targets for antibiotic therapy.

Keywords: bacterial cell wall; murein; muropeptides; penicillin; penicillin‐binding proteins; secretion; cell wall recycling

Figure 1.

Primary structure of peptidoglycan. A polymer of alternating N‐acetylglucosamine (NAG) and N‐acetylmuramic acid (NAM) residues form glycan chains. Adjacent glycan chains are crosslinked via covalent bonds between the peptide side‐chains (every NAM residue has a peptide side‐chain but only two are shown here). The sites of cleavage by muramidases, carboxypeptidases and endopeptidases are indicated by arrows. m‐DAP, meso‐diaminopimelic acid. Adapted from Labischinski and Maidhof .

Figure 2.

The hypothetical ‘tessera’ structure of peptidoglycan. (a) A single tessera is composed of two different glycan chains (rectangles) crosslinked to one another by peptide side‐chains (circles and squares). Note that peptide side‐chains alternate between being in the same plane as the glycan chains and extending above or below the plane because the glycan chain is presumed to form a right‐handed helix. (b) A series of individual tessera formed by multiple crosslinks with adjacent glycan strands. Not all glycan strands are the same length, so imperfections will exist in the hexagonal lattice. NAG residues (white rectangles), NAM residues (light blue rectangles), l‐alanine (dark blue circles), d‐glutamic acid (green circles), meso‐diaminopimelic acid (red squares) and d‐alanine (yellow circles). Adapted from Koch .

Figure 3.

Two models of how peptidoglycan may be arranged in the bacterial cell wall. (a) In the classic horizontal (hoop) model, the polymerised glycan chains lie in the plane of the cell wall (transverse view, red arrow). A rod‐shaped cell is composed of numerous individual hoops side by side (Side view) that are linked to one another by peptide crosslinks (not shown). In this model, the hexagonal array of crosslinked peptidoglycan (shown in Figure b) lies flat and wraps around the surface of the bacterial cell. (b) In the proposed vertical (scaffold) model, the glycan chains extend up and out of the plane of the cell wall (transverse view, red arrow and blue spikes). A complete cell wall is composed of many chains facing outward (Side view, blue spikes) and linked to one another by peptide crosslinks (not shown). The easiest way to envision this model is to rotate the hexagonal array of crosslinked peptidoglycan shown in Figure b by 90°, and then picture the chains of white and blue rectangles (the glycan chains) extending upwards out of the page (e.g. outwards from the surface of a cell). In (b), the extended glycan chains are not drawn to the same scale as the bacterial cell; their extension is exaggerated to illustrate the difference between the horizontal and vertical models.

Figure 4.

Synthesis of N‐acetylglucosamine (as the uridine diphosphate (UDP)‐NAG precursor) and N‐acetylmuramic acid (as the UDP‐NAM precursor). The names and structures of the intermediates leading to NAG and NAM are given in the first two columns. The last column lists the genes encoding the enzymes responsible for each reaction and their cofactors or substrates. Adapted from Raetz and van Heijenoort .

Figure 5.

Synthesis of the peptide side‐chains and disaccharide subunit of peptidoglycan. Amino acids are added sequentially to the lactyl group of N‐acetylmuramic acid (NAM) by enzymes encoded by the genes indicated. The two d‐alanine (d‐Ala) residues are ligated to form a dipeptide and are added to the end of the side‐chain as a single unit. N‐acetylglucosamine (NAG) is added last, just before the entire subunit is translocated across the membrane. l‐ala, l‐alanine; d‐Glu, d‐glutamic acid; m‐DAP, meso‐diaminopimelic acid.

Figure 6.

Recycling pathway of muropeptides released from peptidoglycan. Individual muropeptides are released from peptidoglycan by hydrolysis and acted on by the enzymes indicated. AmpG translocates muropeptides across the cytoplasmic membrane into the cell, where AmpD cleaves off tripeptides. A more complete pathway is described by Park and Uehara (Park and Uehara, ). NAM, N‐acetylmuramic acid; NAG, N‐acetylglucosamine; l‐Ala, l‐alanine; d‐Glu, d‐glutamic acid; m‐DAP, meso‐diaminopimelic acid; d‐Ala, d‐alanine; UDP, uridine diphosphate.

Figure 7.

The basic β‐lactam ring of penicillin and its derivatives, the β‐lactam antibiotics. R1 and R2 indicate sites at which different compounds are added to make a variety of β‐lactam antibiotics.



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Further Reading

Archibald AR, Hancock IC and Harwood CR (1993) Cell wall structure, synthesis, and turnover. In: Sonenshein AL, Hoch JA and Losick R (eds) Bacillus subtilis: And Other Gram‐positive Bacteria: Biochemistry, Physiology, and Molecular Genetics, pp. 381–410. Washington, DC: ASM Press.

Cloud‐Hansen KA, Peterson SB, Stabb EV et al. (2006) Breaching the great wall: peptidoglycan and microbial interactions. Nature Reviews in Microbiology 4: 710–716.

Ghuysen J‐M and Hakenbeck R (eds) (1994) Bacterial Cell Wall. Amsterdam: Elsevier Science.

Goffin C and Ghuysen J‐M (1998) Multimodular penicillin‐binding proteins: an enigmatic family of orthologs and paralogs. Microbiology and Molecular Biology Reviews 62: 1079–1093.

Koch AL (1988) Biophysics of bacterial wall viewed as a stress‐bearing fabric. Microbiological Reviews 52: 337–353.

König H, Claus H and Varma A (2010) Prokaryotic Cell Wall Compounds: Structure and Biochemistry. Heidelberg, Berlin: Springer.

Litzinger S and Mayer C (2010) The murein sacculus. In: König H, Claus H and Varma A (eds) Prokaryotic Cell Wall Compounds: Structure and Biochemistry, pp. 3–52. Heidelberg, Berlin: Springer.

Vollmer W (2008) Structural variation in the glycan strands of bacterial peptidoglycan. FEMS Microbiology Reviews 32: 287–306.

Vollmer W and Seligman SJ (2010) Architecture of peptidoglycan: more data and more models. Trends in Microbiology 18: 59–66.

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Young, Kevin D(Oct 2011) Peptidoglycan. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000702.pub2]