Relevance of the topic and general characteristics of the cell wall
The cell wall is a surface structure of the bacterial cell that determines its shape, protection, and interaction with the host organism. Knowledge of its structure is essential for understanding Gram staining, mechanisms of action of antibiotics (especially β-lactams and glycopeptides), as well as pathogenicity factors.
The core of the cell wall is peptidoglycan (murein). It is present in most bacteria, except for mycoplasmas, which lack a cell wall altogether, and L-forms, which have lost it temporarily or completely.
Structure of peptidoglycan
Peptidoglycan is a mesh-like structure consisting of parallel glycan chains connected by cross-linking peptide bridges.
- Glycan chains are formed by alternating residues of N-acetylglucosamine and N-acetylmuramic acid linked by glycosidic bonds.
- Glycosidic bonds are broken down by lysozyme, an enzyme found in saliva and other secretions that provides non-specific antibacterial defense.
- A tetrapeptide (4 amino acids) extends from N-acetylmuramic acid and connects neighboring glycan chains into a single three-dimensional network via a cross-linking peptide bond.
Knowledge of peptidoglycan structure is important for pharmacology: vancomycin (a glycopeptide antibiotic) binds to the D-alanyl-D-alanine terminus of the peptide bridge, blocking cell wall assembly.
Gram-positive bacteria
In Gram-positive bacteria, the cell wall has a relatively simple structure and includes only two main components:
- A thick peptidoglycan layer (15–18 nm), making up the bulk of the wall.
- Teichoic and lipoteichoic acids attached to the peptidoglycan or anchored in the cytoplasmic membrane via a lipid moiety.
Teichoic acids, like peptidoglycan itself, possess antigenic properties: antibodies are produced against them, which is used in vaccine development and serological diagnostics. The cytoplasmic membrane faces the cytoplasm.
Gram-negative bacteria
The list of medically significant Gram-negative bacteria is much broader, and their cell wall structure is more complex:
- A thin peptidoglycan layer (about 2 nm) located between two membranes.
- The cytoplasmic (inner) membrane composed of phospholipids.
- The outer membrane: the inner layer is phospholipid, and the outer layer contains lipopolysaccharide (LPS). It is linked to the peptidoglycan via lipoprotein.
- Porins are protein channels in the outer membrane through which small hydrophilic metabolites and some antibiotics pass.
- The periplasmic space between the two membranes contains enzymes and transport proteins.
Lipopolysaccharide and its medical significance
LPS is a unique structure of the outer membrane in Gram-negative bacteria, consisting of three parts:
- Lipid A is embedded in the outer membrane, acts as an endotoxin and a major pathogenicity factor; it is released when the bacterium breaks down and causes fever and septic shock.
- The core is a relatively conserved oligosaccharide portion.
- The O-antigen is the outer variable polysaccharide region that determines the bacterial serovar. It is particularly important for identifying Enterobacteriaceae and Shigella.
The character of growth on nutrient media depends on the integrity of LPS synthesis: smooth S-form colonies are formed when the O-antigen is intact, while rough R-form colonies form when it is defective.
Cell-wall-deficient bacteria and L-forms
Not all bacteria have a cell wall. Mycoplasmas lack it initially (hence "plasma" — shapeless, plastic). In contrast, mycobacteria (tuberculosis, leprosy) do have a cell wall, which features a distinct lipid composition.
L-forms are bacteria that have temporarily or irreversibly lost their cell wall due to damaging factors:
- Protoplasts completely lack a cell wall (characteristic of Gram-positive bacteria).
- Spheroplasts retain a partial cell wall (characteristic of Gram-negative bacteria).
The formation of L-forms is triggered by antibiotics that interfere with cell wall synthesis, the excessive action of lysozyme, and other defense factors. The bacterium stops synthesizing the target and becomes resistant. After the factor is removed, reversion can occur — the restoration of the cell wall and a relapse of infection. This explains the chronicity of diseases associated with incomplete antibiotic therapy.
Key points
- The basis of the bacterial cell wall is peptidoglycan made of N-acetylglucosamine and N-acetylmuramic acid, cross-linked by tetrapeptide bridges.
- The glycosidic bonds of peptidoglycan are cleaved by lysozyme; the peptide bridges are the target for vancomycin.
- Gram-positive bacteria feature a thick peptidoglycan layer and teichoic/lipoteichoic acids.
- Gram-negative bacteria feature a thin peptidoglycan layer, an outer membrane with LPS, porins, and a periplasmic space.
- LPS consists of lipid A (endotoxin), the core, and the O-antigen (determines the serovar).
- The integrity of LPS determines the S- or R-form of colonies on nutrient media.
- Mycoplasmas lack a cell wall ab initio, unlike mycobacteria.
- L-forms (protoplasts and spheroplasts) develop under the influence of antibiotics and can cause infectious relapses.