The bacterial cell wall is a tough, specialized layer situated outside the plasma membrane present in the vast majority of bacteria. This protective envelope is unique to bacteria, distinguishing them from animal cells, which lack a cell wall entirely. Its presence is fundamental to bacterial survival, acting as a structural barrier that maintains the cell’s form and integrity against environmental forces. The unique chemical makeup of this layer provides a target for selective intervention, making it a focus in the development of antimicrobial therapies.
The Peptidoglycan Foundation
The foundational structural element common to nearly all bacterial cell walls is a large, mesh-like polymer called peptidoglycan (PG). This molecule forms a continuous sacculus that surrounds the entire cell. Peptidoglycan is a heteropolymer constructed from two alternating amino sugars, N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), which are linked together to form long, linear glycan chains.
Attached to each NAM sugar unit is a short chain of amino acids, typically consisting of three to five residues, forming a peptide stem. The strength of the peptidoglycan layer comes from the cross-linking that occurs between the peptide stems of adjacent glycan chains. These cross-links weave the parallel glycan strands into a single, massive, three-dimensional network. This highly cross-linked structure gives the cell wall its characteristic rigidity and is continuously synthesized and remodeled as the bacterial cell grows and divides.
Essential Functions of the Bacterial Wall
The primary role of the bacterial cell wall is to provide mechanical strength and counteract the significant internal pressure generated by the cell’s cytoplasm. The cytoplasm contains a high concentration of dissolved solutes, making it hypertonic relative to the external environment, causing water to flow into the cell via osmosis. This inward flow of water generates a substantial force, known as turgor pressure, which pushes the plasma membrane outward against the cell wall.
Without the restraining force of the cell wall, this pressure would cause the bacterial cell to swell and burst, a process called osmotic lysis. The rigid peptidoglycan layer prevents this failure, allowing the cell to maintain its structural integrity and characteristic shape, whether rod-shaped, spherical, or spiral. The cell wall also helps regulate the cell’s overall size and is linked to the processes of growth and cell division.
Two Major Architectural Designs
Although the peptidoglycan layer is a shared element, the overall architecture of the bacterial cell wall falls into two distinct categories, differentiated by the Gram staining procedure. Gram-positive bacteria possess a relatively simple structure composed of a single, thick layer of peptidoglycan, which can be 20 to 80 nanometers thick. This dense layer often constitutes up to 90% of the cell wall’s dry weight and is interspersed with accessory polymers like teichoic acids, which contribute to the wall’s rigidity and negative charge.
Gram-negative bacteria exhibit a more complex, multi-layered envelope. They have a much thinner peptidoglycan layer, often only 7 to 8 nanometers thick, which is sandwiched between two lipid bilayers. This periplasmic space contains the peptidoglycan and various proteins. The outermost membrane is unique to this group and contains specialized components, notably lipopolysaccharide (LPS), often referred to as endotoxin due to its role in disease pathogenesis.
This outer membrane acts as an additional permeability barrier, making Gram-negative bacteria more resistant to certain chemical substances and antibiotics. The differences in these architectures explain the Gram stain results. Gram-positive cells retain the initial crystal violet stain because the decolorizing alcohol dehydrates the thick peptidoglycan mesh, trapping the dye. In Gram-negative cells, the alcohol dissolves the outer membrane and washes the crystal violet dye out through the thin peptidoglycan layer, leaving the cells colorless until they are counterstained pink or red with safranin.
Why the Cell Wall is a Key Drug Target
The cell wall’s presence in bacteria but absence in human cells makes the processes involved in its synthesis an excellent target for antimicrobial drugs, allowing for selective toxicity. Beta-lactam antibiotics, which include penicillins and cephalosporins, represent a widely used class of drugs that specifically exploit this structural difference. These antibiotics work by interfering with the final stage of peptidoglycan synthesis, the cross-linking process.
Enzymes known as transpeptidases, also called Penicillin-Binding Proteins (PBPs), are responsible for forming the peptide bridges that link the glycan strands together. The beta-lactam ring structure of the antibiotic mimics the shape of the terminal amino acid sequence that the transpeptidase enzyme recognizes. When the antibiotic binds tightly to the active site of the transpeptidase, it irreversibly inactivates the enzyme, preventing the formation of new cross-links in the growing cell wall.
As the bacteria grow and attempt to divide, the weakened cell wall fails, leading to cell lysis and death. Unfortunately, bacteria can develop resistance, often by producing enzymes called beta-lactamases, which hydrolyze and inactivate the antibiotic’s beta-lactam ring before it can reach its PBP target.