Bacterial Endotoxin Definition: Lipopolysaccharides (LPS), also known as lipoglycans and endotoxins, Endotoxins are part of the outer membrane of the cell wall of Gram-negative bacteria. Although the term “endotoxin” is occasionally used to refer to any cell-associated bacterial toxin, in bacteriology it is properly reserved to refer to the lipopolysaccharide complex associated with the outer membrane of Gram-negative pathogens such as Escherichia coli, Salmonella, Shigella, Pseudomonas, Neisseria, Haemophilus influenzae, Bordetella pertussis and Vibrio cholerae.
The relationship of endotoxin (lipopolysaccharide) to the bacterial cell surface
The biological activity of endotoxin is associated with the lipopolysaccharide (LPS). Toxicity is associated with the lipid component (Lipid A) andimmunogenicity is associated with the polysaccharide components. The cell wall antigens (O antigens) of Gram-negative bacteria are components of LPS. LPS elicits a variety of inflammatory responses in an animal and it activates complement by the alternative (properdin) pathway, so it may be a part of the pathology of Gram-negative bacterial infections.
Endotoxins are mostly found in the outer membrane of Gram-negativebacteria. They are the integral part of the outer cell membraneand are responsible for the organization and stabilityof the bacteria. The general structure of all endotoxinsis a polar heteropolysaccharide chain, with three distinctdomains: the O-antigen region, a core oligosaccharide partand a Lipid A part.
Lipid A is the most conserved part which is responsiblefor the toxicity of endotoxins, while, the effect of polys accharides is negligible. The Lipid A structures werefirst studied based on Enterobacteria. The common architecture of Lipid A is a disaccharide, with glucosamine being the monomer. The two glucosamine monomers arelinked between position 1 and 6, and both of themare phosphorylated to produce bisphosphorylated β-(1-6)-linked glucosamine disaccharide. Furthermore, there arefatty acids ester-linked at positions 3 and 3 and amide linkedat positions 2 and 2. The position 6 is attached to theoligos accharide region.
The oligos accharide moiety is the core unit of LPS. Enteric bacterial LPS cores typically consist of 8–12 sugarunits. Alternative structures are reported for the innercore where the heptose may be substituted by a phosphate,pyrophosphate, or phosphory lethanolamine group. The phosphate groups and charged sugar residues in the innercore and Lipid A are responsible for the stability of LPS byinteractions with cations. Moreover, a diversity of negative lycharged components is also reported, such as one to threeunits of α-3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and hexuronic acid.
The O-specific chain is composed of repetitive subunitsand only exists in smooth-type Gram-negative bacteria.There may be up to 50 identical subunits in an O-chain unit,and each subunit consists of up to eight sugar units. Unlikethe inner core region, the frequent components in O-chainstructures are deoxysugars. There are various O-chainstructures, including linear or branched backbones which aresubstituted by many kinds of aglycones. The O- and Nacetylphosphate and phosphorylethanolamine are commonsubstitutes found. Some non-stoichiometric substitutes mayalso exhibit, such as amino acids, acetamidino groups as wellas formyl groups.
From: Chromatographic Removal of Endotoxins: A Bioprocess Engineer’s Perspective
The physiological activities of LPS are mediated mainly by the Lipid A component of LPS. Lipid A is a powerful biological response modifier that can stimulate the mammalian immune system. During infectious disease caused by Gram-negative bacteria, endotoxins released from, or part of, multiplying cells have similar effects on animals and significantly contribute to the symptoms and pathology of the disease encountered.
Since Lipid A is embedded in the outer membrane of bacterial cells, it probably only exerts its toxic effects when released from multiplying cells in a soluble form, or when the bacteria are lysed as a result of autolysis, complement and the membrane attack complex (MAC), ingestion and killing by phagocytes, or killing with certain types of antibiotics.The injection of living or killed Gram-negative cells or purified LPS into experimental animals causes a wide spectrum of nonspecific pathophysiological reactions, such as fever, changes in white blood cell counts, disseminated intravascular coagulation, hypotension, shockand death. Injection of fairly small doses of endotoxin results in death in most mammals.
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