Эндотоксин липополисахарид и липид А, обнаруженные в клеточной стенке грамотрицательных бактерий

ENDOTOXIN (LIPOPOLYSACCHARIDE) AND LIPID A IN THE GRAM-NEGATIVE CELL WALL Endotoxin is the lipopolysaccharide (LPS) found in the outer membrane of the cell wall of gram-negative bacteria. It is a major topic in #Microbiology, #Immunology, #InfectiousDiseases, and #Pathology because it drives fever, inflammation, and septic shock. The toxic activity of endotoxin lies in its Lipid A component. Endotoxin is released mainly when bacteria die and their cell walls break down, although small amounts are also shed by living, growing cells. LOCATION IN THE CELL WALL: Gram-negative bacteria have a thin peptidoglycan layer surrounded by an outer membrane. The inner leaflet of this membrane is made of phospholipids, while the outer leaflet is made mostly of LPS. This outer membrane acts as a barrier against bile salts, detergents, and many antibiotics, and it explains why gram-negative bacteria are often harder to treat than gram-positive bacteria. Gram-positive bacteria lack LPS. STRUCTURE OF LPS: LPS has three parts: 1. Lipid A: The hydrophobic, membrane-anchoring portion made of a phosphorylated glucosamine disaccharide with fatty acid chains. It is the toxic center of endotoxin and is highly conserved across species. 2. Core polysaccharide: A short sugar chain linked to Lipid A, containing unusual sugars such as KDO (2-keto-3-deoxyoctonate) and heptose. 3. O-antigen (O-polysaccharide): A long, repeating oligosaccharide chain extending outward. It is highly variable between strains and is the basis for serotyping (for example E. coli O157:H7). It is the main target of the antibody response. Bacteria lacking O-antigen form "rough" colonies, while those with it form "smooth" colonies. MECHANISM OF ACTION: Lipid A binds to LPS-binding protein (LBP) in blood, which transfers it to CD14 on macrophages and monocytes. The complex then activates Toll-like receptor 4 (TLR4) with MD-2, triggering NF-kB signaling and release of proinflammatory cytokines such as TNF-alpha, IL-1, and IL-6. Endotoxin also activates the complement cascade (alternative pathway) and the coagulation system (Hageman factor XII). CLINICAL EFFECTS: Fever (through IL-1 and prostaglandin E2 acting on the hypothalamus) Leukopenia followed by leukocytosis Vasodilation, hypotension, and septic shock Disseminated intravascular coagulation (DIC) Tissue damage and multi-organ failure Local Shwartzman reaction in experimental settings KEY CHARACTERISTICS: Endotoxin is heat-stable (it survives autoclaving), weakly immunogenic, cannot be converted into a toxoid, and is less potent than exotoxins on a weight basis. It is not secreted like exotoxins but is part of the cell structure. Common examples of organisms with endotoxin include Escherichia coli, Salmonella, Neisseria meningitidis, Pseudomonas aeruginosa, and Yersinia pestis. DETECTION AND CONTROL: The Limulus amebocyte lysate (LAL) test, made from horseshoe crab blood, detects endotoxin in injectable drugs and medical devices. Treatment of endotoxin-related sepsis relies on rapid antibiotics, fluids, vasopressors, and source control. Polymyxin B binds Lipid A and is used in some settings, but its systemic toxicity limits use. #Endotoxin #Lipopolysaccharide #LipidA #GramNegativeBacteria #SepticShock #TLR4 #MedicalMicrobiology #MedStudents #USMLE #Immunology