Endotoxins: relationships between structure, function, and activity.
Molecules of endotoxin (lipopolysaccharides, LPS), forming a unique molecular class with peculiar physico-chemical properties, impart a very important role in the formation and function of the outer membrane (OM). The latter is strictly asymmetric with the LPS monolayer forming the outer leaflet and the phospholipid (PL) monolayer forming the inner leaflet. Thus, the OM builds a functional lipid environment for the OM proteins (Omp's, porins) and the LPS layer is the first locus of interaction of the bacterial cells with components of the host's immune system,. Therefore its physical state and biochemical parameters (such as the fluidity of the lipid A acyl chains and the backbone charge density) essentially influence the defense of bacteria against the attack of the human immune systems such as the complement and antimicrobial peptides/proteins. LPS, released from the bacterial cell, is responsible for a variety of biological effects which can be ascribed to the unique structural features of LPS- the three-dimensional supramolecular structure and the intramolecular conformation - which are essential determinants of the bioactivity of endotoxins. Here, the physico-chemical parameters which are important on the one side for the function of the OM and on the other side for the activity of isolated LPS are reviewed.
Brandenburg
Klaus
K
Forschungszentrum Borstel, LG Biophysik, Parkallee 10, D-23845 Borstel, Germany. kbranden@fz-borstel.de
Wiese
Andre
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D008070:Lipopolysaccharides