Peptidoglycan: Structure, Function

Last updated on June 3rd, 2021

The term peptidoglycan was derived from the peptides and the sugars (glycan) that make a molecule; it is also called ‘murein’ or ‘mucopeptide’. This is a complex interwoven network of sugar polymer and amino acids, that surrounds the entire bacterial cell. It provides structural rigidity and gives characteristics shape for that bacteria.

Peptidoglycan is found only in bacterial cell walls but not in human cells. Peptidoglycan is a good target for antibacterial drugs such as penicillins, cephalosporins, and vancomycin, which inhibit the synthesis of peptidoglycan by inhibiting transpeptidase reactions.

Penicillins and cephalosporins are not effective for Mycoplasma pneumoniae as it lacks cell wall (peptidoglycan).

Structure of Peptidoglycan

Peptidoglycan consists of carbohydrate backbone (glycan chain) composed of alternating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) molecules attached through β-1,4-glycosidic bonds. The covalent bonds between NAG-NAM form a sheet-like structure around the bacterium. There are multiple such sheet-like structures that are cross-linked with each other by tetrapeptides. This cross-linking provides rigidity to the bacterial cell, the strength of which depends on the frequency of cross-links present.

Each muramic acid of a glycan chain contains a tetrapeptide consisting of both D- and L- amino acids. L-alanine, D-glutamic acid, either lysine or its structural analog diaminopimelic acid (DAP), and D-alanine are found in those tetrapeptides.

Presence of two amino acids of the D stereoisomer; D -alanine, and D -glutamic acid, is the unique feature of peptidoglycan. Proteins, by contrast, always consist of L -amino acids.

In gram-negative bacteria such as Escherichia coli, peptidoglycan cross-linkage occurs by a peptide bond formed between DAP and the terminal D-alanine of another glycan chain.

In gram-positive bacteria, cross-linkage may occur through a short peptide inter-bridge (e.g., glycine inter-bridge in Staphylococcus aureus) between L-lysine of one glycan chain and the D-alanine on the adjacent glycan chain.

Diversity of Peptidoglycan

Gram positive and gram negative cell wall
Difference between Gram positive and Gram Negative bacterial cell wall

Peptidoglycan is the outermost cell-wall layer of gram-positive bacteria. In gram-negative bacteria, additional layers are present outside this rigid layer, called lipopolysaccharide. The peptidoglycan layer is much thicker in gram-positive than in gram-negative bacteria. In gram-positive bacteria, as much as 90% of the cell wall is peptidoglycan whereas, in gram-negative bacteria, it is only about 10%.

Teichoic acid and lipoteichoic acid in Peptidoglycan layer
Gram Positive Cell wall with Teichoic acid

Many Gram-positive bacteria also have teichoic acid and lipoteichoic acid which are polymers of either glycerol phosphate or ribitol phosphate. Lipoteichoic acid penetrates the peptidoglycan layer and is covalently linked to the lipid in the cytoplasmic membrane, whereas teichoic acids mostly anchor to the muramic acid of the peptidoglycan.

Unique amino acids and sugars found in peptidoglycan layer

  • N-acetylmuramic acid and diaminopimelic acid are unique to bacterial cells and never been found in the cell walls of Archaea or Eukarya.
  • Amino acids of the D stereoisomer: D -alanine, and D -glutamic acid are not found in animal proteins.
Peptidoglycan structure of E. coliPeptidoglycan structure of Staphylococcus aureus Source:
Peptidoglycan layer of Gram-negative (left) and Gram-positive bacteria (right)


  1. Peptidoglycan provides rigid support to bacterial cells and maintains the characteristic shape of the cell.
  2. Allows bacterial cells to withstand media of low osmotic pressure, such as water.
  3. Bacteria are divided into two majors groups, called gram-positive and gram-negative based on Gram-stain reaction. The difference in the cell-wall structure (thickness of the peptidoglycan layer) plays a major role in the differential staining reactions of bacteria.

Medical Significance

  • Peptidoglycan is a good target for antibacterial drugs.  Drugs like penicillins, cephalosporins, etc inhibit transpeptidase reaction (which makes cross-links between the two adjacent tetrapeptides) involved in peptidoglycan synthesis.
  • Lysozyme enzymes present in human tears, mucus, and saliva cleave peptidoglycan backbone breaking the glycosyl bonds of peptidoglycan, thus providing a major line of defense against bacterial infection.
  • Gram-positive bacteria are generally resistant to complement-mediated lysis because the thick peptidoglycan layer in their cell wall prevents insertion of the membrane attack complex (MAC) into the inner membrane.

References and further readings

  1. Madigan Michael T, Bender, Kelly S, Buckley, Daniel H, Sattley, W. Matthew, & Stahl, David A. (2018). Brock Biology of Microorganisms (15th Edition). Pearson.

About Acharya Tankeshwar 476 Articles
Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. I am working as an Asst. Professor and Microbiologist at Department of Microbiology and Immunology, Patan Academy of Health Sciences, Nepal. If you want me to write about any posts that you found confusing/difficult, please mention in the comments below.

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