The peptidoglycans are the major components of the cell wall of bacteria. They are also known as "murein sacs" or simply "murein" and their characteristics divide bacteria into two large groups: gram-negative and gram-positive.
Gram-negative bacteria are distinguished by the fact that they have a peptidoglycan layer between their inner and outer cell membranes, while gram-positive bacteria also have a layer of this compound, but it is located only on the outer part of the plasma membrane.
Schematic of the structure of peptidoglycan in E. coli (Source: Yikrazuul / Public domain via Wikimedia Commons)
In gram-negative bacteria, peptidoglycan occupies about 10% of the cell wall, in contrast to gram-positive bacteria, the peptidoglycan layer can occupy about 90% of the cell wall.
The "network" type structure formed by peptidoglycan molecules is one of the factors that gives bacteria great resistance to external agents. Its structure consists of long chains of glycans that associate to form an open network that covers the entire cytosolic membrane.
The chains of this macromolecule have an average length of 25 to 40 units of attached disaccharides, although species of bacteria have been found to possess disaccharide chains of more than 100 units.
Peptidoglycan also participates in the transport of molecules and substances from the intracellular space to the extracellular environment (the surface), since the precursor molecules of this compound are synthesized inside the cytosol and are exported to the outside of the cell.
Synthesis of peptidoglycans
The synthesis of peptidoglycan involves more than twenty different reactions, which occur in three different places in the bacterial cell. The first part of the process is where the peptidoglycan precursors are generated and this occurs in the cytosol.
On the inner face of the cytosolic membrane, the synthesis of lipid intermediates occurs and the last part, where the polymerization of peptidoglycans occurs, occurs in the periplasmic space.
Process
The precursors uridine-N-acetylglucosamine and uridine-N-acetylmuramic acid are formed in the cytoplasm from fructose-6-phosphate and through reactions catalyzed by three transpeptidase enzymes that act consecutively.
The assembly of the pentapeptide chains (L-alanine-D-glutamine-diaminopimelic acid-D-alanine-D-alanine) is produced in a stepwise manner by the action of ligase enzymes that add step by step the amino acid alanine, a residue of D-glutamine, another from diaminopimelic acid and another dipeptide D-alanine-D-alanine.
An integral membrane protein called phospho-N-acetylmuramyl-pentapeptide-transferase, which is located on the inside, catalyzes the first synthesis step in the membrane. This performs the transfer of uridine-N-acetylmuramic acid from the cytoplasm to bactoprenol (a hydrophobic lipid or alcohol).
Bactoprenol is a transporter associated with the inner face of the cell membrane. When uridine-N-acetylmuramic acid binds to bactoprenol, the complex known as lipid I is formed. Then a transferase adds a second molecule, the pentapeptide, and a second complex known as lipid II is formed.
Lipid II is then composed of uridine-N-acetylglucosamine, uridine-N-acetylmuramic acid, L-alanine, D-glucose, diaminopimelic acid and the dipeptide D-alanine-D-alanine. Finally, in this way the precursors are incorporated into the macromolecular peptidoglycan from the cell exterior.
The transport of lipid II from the inner to the inner face of the cytoplasm is the last step in the synthesis and is catalyzed by an enzyme "muramic flipase", which is responsible for incorporating the newly synthesized molecule into the extracellular space where it will crystallize.
Structure
Peptidoglycan is a heteropolymer made up of long carbohydrate chains that intersect with short peptide chains. This macromolecule surrounds the entire external surface of the bacterial cell, has a "solid mesh" and integral shape, but is characterized by a great elastic capacity.
The carbohydrate or carbohydrate chains are made up of repeats of disaccharides that alternately contain amino sugars such as N-acetylglucosamine and N-acetylmuramic acid.
Graphical approach to the lattice structure of peptidoglycan (Source: Bradleyhintze / CC0 via Wikimedia Commons)
Each disaccharide binds to the other through a β (1-4) type glycosidic bond, which is formed in the periplasmic space by the action of a transglycosylase enzyme. Between gram-negative and gram-positive bacteria there are differences in the order of the components that are part of the peptidoglycan.
Peptidoglycan in gram negative cell
Peptidoglycan has in its structure a D-lactyl group attached to N-acetylmuramic acid, which allows the covalent anchoring of short peptide chains (generally with a length of two to five amino acids) through an amide bond.
Peptidoglycan in gram positive cell
The assembly of this structure occurs in the cell cytoplasm during the first phase of peptidoglycan biosynthesis. All peptide chains that are formed have amino acids in the D and L configuration, which are synthesized by racemase enzymes from the L or D form of the corresponding amino acid.
All peptidoglycan chains have at least one amino acid with dibasic characteristics, as this allows the network between adjacent chains of the cell wall to form and interlock.
Features
Peptidoglycan possesses at least 5 main functions for bacterial cells, namely:
- Protect the integrity of cells against internal and / or external changes in osmotic pressure, also allowing bacteria to withstand extreme changes in temperature and survive in hypotonic and hypertonic environments with respect to their interior.
- Protect the bacterial cell from the attack of pathogens: the rigid peptidoglycan network represents a physical barrier that is difficult to overcome for many external infectious agents.
- Maintains cell morphology: many of the bacteria take advantage of their particular morphology to have a larger surface area and in turn to be able to acquire a greater quantity of the elements that participate in their metabolism to generate energy. Many bacteria live under incredible external pressures and maintaining their morphology is essential to be able to survive in such conditions.
- It acts as a support for many structures that are anchored to the cell wall of bacteria. Many structures, such as cilia, for example, need a firm anchor in the cell, but that at the same time gives them the ability to move in the extracellular environment. The anchorage inside the cell wall allows the cilia this particular mobility.
- Regulates growth and cell division. The rigid structure that means the cell wall represents a barrier for the cell to have a limited expansion to a specific volume. It also regulates that cell division does not occur in a disorderly way throughout the cell, but rather occurs at a specific point.
References
- Helal, AM, Sayed, AM, Omara, M., Elsebaei, MM, & Mayhoub, AS (2019). Peptidoglycan pathways: there are still more. RSC advances, 9 (48), 28171-28185.
- Quintela, J., Caparrós, M., & de Pedro, MA (1995). Variability of peptidoglycan structural parameters in gram-negative bacteria. FEMS microbiology letters, 125 (1), 95-100.
- Rogers, HJ (1974). Peptidoglycans (muropeptides): structure, function, and variations. Annals of the New York Academy of Sciences, 235 (1), 29-51.
- Vollmer, W. (2015). Peptidoglycan. In Molecular Medical Microbiology (pp. 105-124). Academic Press.
- Waldemar Vollmer, Bernard Joris, Paulette Charlier, Simon Foster, Bacterial peptidoglycan (murein) hydrolases, FEMS Microbiology Reviews, Volume 32, Issue 2, March 2008, Pages 259–286.