A case for an endotoxic conformation

Gram-negative bacteria express on their surface endotoxins which are essential for bacterial growth and survival. If released from the bacterial cell, endotoxins induce, in higher organisms, a variety of pathophysiological effects known as manifestations of bacterial sepsis. Chemically, endotoxins are lipopolysaccharides (LPS) composed of a polysaccharide and a lipid component, termed lipid A, which is responsible for the induction of endotoxin effects. Lipid A of all endotoxically active LPS have a similar architecture. The structural and conformational parameters endowing lipid A with its potent bioactivity have been well characterized. The toxic effects of endotoxins or their lipid A component, respectively, are initiated by the specific interaction of lipid A with macrophages/monocytes resulting in the production of peptide or lipid mediators like tumor necrosis factor alpha (TNF), the leukotrienes, and oxygen radicals. This interaction requires a unique "endotoxic conformation" of lipid A on the one hand, and specific cellular receptors on the other. The interaction and subsequent mediator production can be specifically and antagonistically inhibited by lipid A partial structures.