Understanding endotoxin
In gram-negative bacteria, there are two membranes: the inner membrane (IM) and the outer membrane (OM). The inner membrane is very similar to the plasma membrane of eukaryotic cells that is composed of a phospholipid bilayer. The outer membrane serves as a protective structure to the bacteria and is made up of asymmetrical lipid structures including lipopolysaccharides (LPS). When talking of endotoxins, people are referencing the biological activity of LPS once it is removed from the OM.
The LPS itself has 2 major components: hydrophobic lipid A and hydrophilic polysaccharide (O-antigen). The lipid A structure is the membrane-anchoring region of the LPS and is highly conserved in bacteria. The O-antigen refers to strands of oligosaccharide subunits that are attached to the core polysaccharide. Oligosaccharide subunits are made of 3-5 sugars and ranges to 40 repeating units (usually longer than the core polysaccharide) and have a major antibody-combining site that cecropins interact with. A fun fact about these oligosaccharides is that the sugars that comprise them are characteristically dideoxyhexoses, which only naturally occur in gram-negative bacteria.
In terms of toxicity, both lipid A and polysaccharide side chains contribute to virulence. Lipid A is the toxic section of the LPS while the polysaccharides are nontoxic and immunogenic. LPS binds to lipid binding proteins which eventually causes inflammation which activates the complement and coagulation cascades. When this biological activity is at a high enough rate, it can cause septic shock.
10-15% of sepsis patients have septic shock from high activity of endotoxins (endotoxin septic shock; ESS), adding up to 5-7 million cases globally each year. Mortality is correlated to the level of endotoxins within the blood (endotoxemia). ESS patients can be treated with anti-endotoxin therapy via antibiotics like polymyxin B hemadsorption that bind and inhibit endotoxins. Research is continuing to be done to develop more effective therapies to treat gram-negative bacterial infections.
Sources:
https://www.sciencedirect.com/science/article/pii/S2452316X17300406
https://link.springer.com/article/10.1186/s13054-023-04690-5
