Peptidoglycans are large macromolecules forming a mesh-like layer that encases the bacterial cytoplasmic membrane. Composed of sugars and amino acids, these structures are a defining feature of most bacterial cell walls. They provide structural support and protection against environmental stresses.
Building the Bacterial Wall
Peptidoglycans form a continuous, mesh-like sacculus within the bacterial cell wall. The sugar component consists of alternating units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM), linked by β-(1,4)-glycosidic bonds. Attached to each N-acetylmuramic acid residue is a short oligopeptide chain, made of three to five amino acids. These peptide chains cross-link with those from other strands, creating a three-dimensional, interconnected mesh.
The thickness and composition of this peptidoglycan layer vary significantly between different types of bacteria, a difference used in Gram staining to classify them as either Gram-positive or Gram-negative. Gram-positive bacteria possess a thicker peptidoglycan layer, ranging from 20 to 80 nanometers, which can constitute 40% to 90% of the cell wall’s dry weight. This thick, multi-layered structure allows Gram-positive bacteria to retain crystal violet stain, appearing purple under a microscope. In contrast, Gram-negative bacteria have a thinner peptidoglycan layer, 7 to 8 nanometers thick, and it is a single layer. Gram-negative bacteria also possess an outer lipid membrane that covers their thin peptidoglycan layer.
Why Peptidoglycans are Crucial
Peptidoglycans are essential for bacterial survival, fulfilling several functions. The cross-linked mesh provides structural integrity and helps maintain the bacterial cell’s shape. This rigid framework acts as an exoskeleton, providing strength to the bacterial cell.
Beyond maintaining shape, the peptidoglycan layer protects the bacterium from osmotic lysis, the bursting of the cell in environments with lower solute concentration. The internal pressure within a bacterial cell, known as turgor pressure, can be substantial. The peptidoglycan wall resists this pressure, preventing the cell from rupturing. It also functions as a physical barrier, shielding the bacterial cell from environmental threats.
Targeting Peptidoglycans with Antibiotics
The unique structure of peptidoglycans makes them an ideal target for antibiotics, as mammalian cells lack this component. Antibiotics like penicillin and other beta-lactams disrupt peptidoglycan layer synthesis. These antibiotics interfere with penicillin-binding proteins (PBPs), enzymes involved in the final stages of peptidoglycan synthesis, specifically the cross-linking of peptide chains.
By inhibiting these cross-linking reactions, beta-lactam antibiotics prevent proper bacterial cell wall assembly, leading to a weakened structure. This compromised wall cannot withstand internal osmotic pressure, causing the cell to swell and burst. Glycopeptides such as vancomycin also target peptidoglycan synthesis but through a different mechanism; they bind to the D-alanyl-D-alanine terminus of peptidoglycan precursors, preventing new units from being added to the growing chain. This action halts cell wall construction, particularly impacting Gram-positive bacteria due to their thicker peptidoglycan layer.
How the Body Detects Peptidoglycans
The human immune system detects foreign invaders like bacteria, and peptidoglycans serve as “Pathogen-Associated Molecular Patterns” (PAMPs). These conserved molecular structures are found on microbes but not on host cells, signaling infection. The innate immune system, the body’s first line of defense, recognizes peptidoglycans through specialized receptors.
Specific receptors, such as Nod-like receptors (NLRs) like NOD1 and NOD2, are present within mammalian cells and sense peptidoglycan fragments. Upon detection, these receptors trigger intracellular signaling pathways that activate transcription factors, leading to the expression of genes associated with inflammatory and antimicrobial responses. This recognition initiates an immune response, including the release of cytokines, which are signaling molecules that help coordinate the body’s defense against bacterial infections.