Peptidoglycan

Kevin D Young, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

Published online: October 2011

DOI: 10.1002/9780470015902.a0000702.pub2

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 (1994).
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 (1998).
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 2b) 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 2b 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 (1996) and van Heijenoort (1996).
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, 2008). 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 -lactam ring of penicillin and its derivatives, the -lactam antibiotics. R1 and R2 indicate sites at which different compounds are added to make a variety of -lactam antibiotics.
close
 References
    Barreteau H, Kovac A, Boniface A et al. (2008) Cytoplasmic steps of peptidoglycan biosynthesis. FEMS Microbiology Reviews 32: 168–207.
    Begg KJ, Takasuga A, Edwards DH et al. (1990) The balance between different peptidoglycan precursors determines whether E. coli cells will elongate or divide. Journal of Bacteriology 172: 6697–6703.
    Bouhss A, Trunkfield AE, Bugg TDH and Mengin-Lecreulx D (2008) The biosynthesis of peptidoglycan lipid-linked intermediates. FEMS Microbiology Reviews 32: 208–233.
    Clarke TB, Davis KM, Lysenko ES et al. (2010) Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nature Medicine 16: 228–231.
    Denome SA, Elf PK, Henderson TA, Nelson DE and Young KD (1999) E. coli mutants lacking all possible combinations of eight penicillin binding proteins: viability, characteristics, and implications for peptidoglycan synthesis. Journal of Bacteriology 181: 3981–3993.
    Dijkstra AJ and Keck W (1996) Peptidoglycan as a barrier to transenvelope transport. Journal of Bacteriology 178: 5555–5562.
    Dmitriev B, Toukach F and Ehlers S (2005) Towards a comprehensive view of the bacterial cell wall. Trends in Microbiology 13: 569–574.
    Gan L, Chen S and Jensen GJ (2008) Molecular organization of Gram-negative peptidoglycan. Proceedings of the National Academy of Sciences of the USA 105: 18953–18957.
    Glauner B (1988) Separation and quantification of muropeptides with high-performance liquid chromatography. Analytical Biochemistry 172: 451–464.
    book Hakenbeck R, Brückner R and Henrich B (2010) "Cell wall targeted antibiotics". In: König H, Claus H and Varma A (eds) Prokaryotic Cell Wall Compounds: Structure and Biochemistry, pp. 347–381. Heidelberg, Berlin: Springer.
    Hayhurst EJ, Kailas L, Hobbs JK and Foster SJ (2008) Cell wall peptidoglycan architecture in Bacillus subtilis. Proceedings of the National Academy of Sciences of the USA 105: 14603–14608.
    book van Heijenoort J (1996) "Murein synthesis". In: Neidhardt FC, Curtiss R III and Ingraham JL et al. (eds) E. coli and Salmonella typhimurium: Cellular and Molecular Biology, 2nd edn, vol. 1, pp. 1025–1034. Washington, DC: ASM Press.
    Höltje J-V (1998) Growth of the stress-bearing and shape-maintaining murein sacculus of E coli. Microbiology and Molecular Biology Reviews 62: 181–203.
    Koch AL (1990) Additional arguments for the key role of ‘smart’ autolysins in the enlargement of the wall of Gram-negative bacteria. Research in Microbiology 141: 529–541.
    Koch AL (1998) Orientation of the peptidoglycan chains in the sacculus of E. coli. Research in Microbiology 149: 689–701.
    Koch AL (2000) Simulation of the conformation of the murein fabric: the oligoglycan, penta-muropeptide, and cross-linked nona-muropeptide. Archives of Microbiology 174: 429–439.
    Kraus W and Höltje J-V (1987) Two distinct transpeptidation reactions during murein synthesis in E. coli. Journal of Bacteriology 169: 3099–3103.
    book Labischinski H and Johannsen L (1986) "On the relationships between conformational and biological properties of murein". In: Seidl PH and Schleifer KH (eds) Biological Properties of Peptidoglycan, pp. 37–42. Berlin: Walter de Gruyter.
    book Labischinski H and Maidhof H (1994) "Bacterial peptidoglycan: overview and evolving concepts". In: Ghuysen J-M and Hakenbeck R (eds) Bacterial Cell Wall, pp. 23–38. Amsterdam: Elsevier Science.
    Lam H, Oh DC, Cava F et al. (2009) D-amino acids govern stationary phase cell wall remodeling in bacteria. Science 325: 1552–1555.
    Meroueh SO, Bencze KZ, Hesek D et al. (2006) Three-dimensional structure of the bacterial cell wall peptidoglycan. Proceedings of the National Academy of Sciences of the USA 103: 4404–4409.
    Park JT and Uehara T (2008) How bacteria consume their own exoskeletons (turnover and recycling of cell wall peptidoglycan). Microbiology and Molecular Biology Reviews 72: 211–227 and table of contents.
    book Raetz CRH (1996) "Bacterial lipopolysaccharides: a remarkable family of bioactive macroamphiphiles". In: Neidhardt FC, Curtiss R III and Ingraham JL et al. (eds) E. coli and Salmonella typhimurium: Cellular and Molecular Biology, 2nd edn, vol. 1, pp. 1035–1063. Washington, DC: ASM Press.
    Royet J and Dziarski R (2007) Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences. Nature Reviews in Microbiology 5: 264–277.
    Satta G, Fontana R and Canepari P (1994) The two-competing site (TCS) model for cell shape regulation in bacteria: the envelope as an integration point for the regulatory circuits of essential physiological events. Advances in Microbial Physiology 36: 181–245.
    Sauvage E, Kerff F, Terrak M, Ayala JA and Charlier P (2008) The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiology Reviews 32: 234–258.
    Scheurwater EM and Burrows LL (2011) Maintaining network security: how macromolecular structures cross the peptidoglycan layer. FEMS Microbiology Letters 318: 1–9.
    Schleifer KH and Kandler O (1972) Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriological Reviews 36: 407–477.
    Tomasz A (1979) The mechanism of the irreversible antimicrobial effects of penicillins: how the beta-lactam antibiotics kill and lyse bacteria. Annual Review of Microbiology 33: 113–137.
    Vollmer W and Höltje J-V (2004) The architecture of the murein (peptidoglycan) in Gram-negative bacteria: vertical scaffold or horizontal layer(s)? Journal of Bacteriology 186: 5978–5987.
    Vollmer W, Blanot D and de Pedro MA (2008) Peptidoglycan structure and architecture. FEMS Microbiology Reviews 32: 149–167.
    Young KD (2006) Too many strictures on structure. Trends in Microbiology 14: 155–156.
    Zapun A, Contreras-Martel C and Vernet T (2008) Penicillin-binding proteins and -lactam resistance. FEMS Microbiology Reviews 32: 361–385.
 Further Reading
    book 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.
    book 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.
    book König H, Claus H and Varma A (2010) Prokaryotic Cell Wall Compounds: Structure and Biochemistry. Heidelberg, Berlin: Springer.
    book 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.

Related Sub-Topics:

Structure of Cell–Cell Interactions | Cell Signalling | Other Biomolecules: Structure, Function, Metabolism | Cell Structure | Composition and Structure of Microbial Cells | Bacteria | Medical Microbiology
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Peptidoglycan
 
How to Cite close
Young, Kevin D(Oct 2011) Peptidoglycan. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000702.pub2]