Overview
Endotoxin refers to the lipopolysaccharide component of the outer membrane of Gram‑negative bacteria. When these bacteria lyse or shed membrane blebs, endotoxin is released and can provoke strong inflammatory responses in animals.
Explanation
The endotoxin molecule consists of three parts: lipid A, a core oligosaccharide and a repeating O‑antigen polysaccharide. Lipid A anchors the molecule in the bacterial membrane and is the biologically active component responsible for most toxic effects. The core region and O antigen vary among species and contribute to antigenic diversity. During infection or antibiotic treatment, endotoxin is released into host tissues and enters the circulation. Immune cells recognize lipid A via pattern‑recognition receptors such as toll‑like receptor 4 and CD14, leading to activation of nuclear factor‑κB and production of cytokines including tumor necrosis factor‑α and interleukin‑1. This cascade causes fever, vasodilation, coagulation abnormalities and, in high amounts, septic shock. Unlike exotoxins, endotoxin is not a secreted protein and cannot be converted to a toxoid. It is heat stable, withstands autoclaving, and its activity can only be neutralized by specific antibodies or removal. Detection of endotoxin contamination in injectable pharmaceuticals relies on the Limulus amebocyte lysate assay, which uses horseshoe crab blood clotting factors sensitive to lipid A.
Mechanisms and clinical effects
Gram‑negative pathogens such as Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa and Neisseria meningitidis owe much of their endotoxicity to lipid A. Endotoxin contributes to the pathophysiology of meningococcemia and sepsis by inducing systemic inflammatory response and disseminated intravascular coagulation. In neonatal intensive care units, contaminated intravenous fluids can cause endotoxin‑mediated fever. Bacterial blebs containing endotoxin have been explored as vaccine components; detoxified lipid A derivatives (monophosphoryl lipid A) serve as adjuvants. Understanding the structural determinants of endotoxin and host receptor interactions informs development of therapeutic antagonists and improved sepsis management.
Endotoxin is a structural component of Gram‑negative bacteria that becomes toxic only when liberated from the cell wall. Awareness of its properties and biological effects is critical for laboratory safety, clinical diagnosis and pharmaceutical quality control.
Related Terms: Lipopolysaccharide, Exotoxin, Gram-negative bacteria, Septic shock, Toll-like receptor 4