Peptidoglycan is a complex polymer found in the cell wall of bacteria. It is comprised of amino acids attached to sugars, linked together by peptide bonds. Along with lipoteichoic acid and teichoic acid, important secondary cell wall polymers, it forms a part of a “mural” or “lattice” that covers the cell wall or surrounds the bacterial cell [1]. Bacterial peptidoglycan varies widely in structure depending on the amino acid sequence, types of cross-links, and presence or absence of secondary modifications in both the glycan strands and peptides [2]. Peptidoglycan serves the following purposes:

1. Provides Structure to the Cell

Peptidoglycan is a polymer composed of sugars and amino acids. When many molecules of peptidoglycan are joined together, they form an orderly crystal lattice structure, which contributes to the strength of the cell [1]. Peptidoglycan also works to counteract the osmotic pressure from cytoplasm. Contrary to popular belief, peptidoglycan does not actually give bacterial cells their shape [3], but rather reinforce the strength of the cell. In addition, bacteria are classified as being either Gram-positive or Gram-negative based on differences in the quantity and structure of peptidoglycan in the cell wall.

2. It Is Involved in Binary Fission

In binary fission, the cell wall is broken into two sections. Once one section of the bacterial cell wall has been breached, the cell begins to divide until all its volume is filled with daughter cells.

The two sections then come together to form a membrane sac allowing further division. This process happens in most bacteria and, more importantly, is how most bacteria reproduce themselves. For the cell wall to break, Peptidoglycan continues to grow as the cell elongates. It then completes the cell wall after the cells get split.

3. Safeguards the Cytoplasmic Membrane

The cytoplasmic membrane is a semi-permeable membrane that lies inside the cell wall. It allows for nutrient intake and waste removal. Peptidoglycan helps to form the covering for the wall of the cytoplasmic membrane as well as counteract the osmotic pressure from the cytoplasmic membrane so that bacteria can keep their internal environment stable.

4. Counteracting the Osmotic Pressure of the Cytoplasm

The cytoplasm is a mixture of proteins, carbohydrates, salts, sugars, amino acids, and nucleotides. Because the cytoplasm contains so many dissolved nutrients from the result of active transport, bacteria tend to be hypertonic compared to their surrounding areas [6] (meaning that the cell will naturally want to take in water to dilute this highly concentrated cytoplasmic solution). Osmotic pressure is the pressure caused by the dissolved particles’ concentration difference between the cytoplasm and the surroundings of the cell [5]. Because the cytoplasm is such a large amount of salt, this can cause the cell to collapse if it doesn’t have any way to counteract it. It does this by secreting a ton of water from its outer membrane, which comes from outside and pushes back against the cytoplasmic membrane. The peptidoglycan acts to push back against the osmotic pressure that would eventually cause the cell to undergo cytolysis and burst [6].

5. Protects the Cell Against Antibiotics

Peptidoglycan is much thicker in Gram-positive bacteria than it is in Gram-negative bacteria [1]. This is why bacteria can be classified as Gram-negative or Gram-positive. Penicillin works to inhibit peptidoglycan synthesis in bacterial cell which results in cell death.

Peptidoglycan in Non-Tuberculous Mycobacteria

Non-tuberculous mycobacteria (NTM) are present throghout our environment, though NTM diseases are not common as NTM is considered to be less virulent than Mycobacterium tuberculosis. However, chronic respiratory mycobacterial infections with nontuberculous mycobacteria are increasing in incidence and are notoriously difficult to treat.

NTM are characterized by a thin peptidoglycan layer surrounded by a thick outer lipid-rich coating that enables NTM attachment to rough surfaces and by offering resistance to antibiotics and disinfectants, helping NTM survival in low oxygen and carbon concentrations and in other adverse conditions [7].

NTM bacteria treatment for nontuberculous mycobacterial lung disease is challenging since the potency of available agents is relatively low, resistance to antibacterial agents is common and prolonged treatment with multiple drugs is difficult to tolerate.

At Crestone, Inc., we are developing a novel class of anti-mycobacterial agents (benzothiazole amides) that target the MmpL3 protein essential for cell wall synthesis. In collaboration with scientists at Colorado State University, the hit-to-lead program has resulted in CRS0393, an advanced compound that shows excellent potency against all mycobacteria tested, including multidrug-resistant strains–meaning it is promising when it comes to nontuberculous mycobacteria treatment.

In regards to mycobacterial infections, it’s interesting to note that mycobacteria are difficult to stain by Gram’s method, however, they are usually considered Gram-stain positive [8].

Final Words

Peptidoglycan plays an important role in the cell wall of bacteria and is an important target for many antibiotics. In order to combat bacterial resistance, new tools to fight infectious diseases are needed.


  1. Editors, BD. “Peptidoglycan (Murein) – Definition, Structure & Function.” Biology Dictionary, 29 Apr. 2017,
  2. Vollmer, Waldemar. “Peptidoglycan.” Peptidoglycan – an Overview | ScienceDirect Topics, 2015,
  3. Libretexts. “6.6.4: Peptidoglycan Synthesis and Cell Division.” Biology LibreTexts, Libretexts, 24 Apr. 2020,
  4. Newman, Tim, and Zara Risoldi Cochrane. “Penicillin: Function, History, and Resistance.” Medical News Today, MediLexicon International, 30 July 2018,
  5. “Tonicity: Hypertonic, Isotonic & Hypotonic Solutions (Article).” Khan Academy, Khan Academy,
  6. Kaiser, Gary. “2.3: The Peptidoglycan Cell Wall.” Biology LibreTexts, Libretexts, 9 Apr. 2022,
  7. Sharma, Surendra K.; Upadhyay, Vishwanath. Epidemiology, diagnosis & treatment of non-tuberculous mycobacterial diseases. Indian Journal of Medical Research 152(3):p 185-226, September 2020. | DOI: 10.4103/ijmr.IJMR_902_20
  8. “Non-Tuberculous Mycobacteria: Molecular and Physiological Bases of Virulence and Adaptation to Ecological Niches.” PubMed Central, National Library of Medicine, 9 Sep 2020,