Structure, Function and Biological Activity of Lipopolysaccharide Lipid A

Abstract

Bacterial lipopolysaccharides (LPS) are the major outer surface membrane components present in almost all gram-negative bacteria. It consists of poly- or oligosaccharide region that is anchored in the outer membrane by a specific lipid moiety termed lipid A. Recent studies have shown that it is only the lipid A of LPS that has the function of endotoxin. Despite its general structural conservation, lipid A also has considerable structural microheterogeneity which can vary depending on diverse factors including bacterial adaptation to changing environment and external stimuli, incomplete biosynthesis, and breakdown products and/or chemical modifications. Therefore it is more appropriate to consider lipid A as a family of structurally related molecular species with different acylation and phosphorylation patterns rather than as an individual, homogeneous molecule. The studies of structure-function relationship of lipid A, which has the typical structure of E. coli type lipid A backbone, demonstrated that activities differed depending on: 1) the number of phosphoryl and acyl residues, 2) the substituted site of phosphoryl and acyl residues, 3) the chain length of acyl residues, 4) lipid A conformation. Current investigations showed that lipid A and also the integral outer membrane proteins responsible for the final stage of LPS transport are the pinpoints in solving the problem of bacterial drug resistance. The identification of inhibitors that specifically target LPS transport in vitro and more importantly in vivo have a significant potential for the development of novel drugs against multi-drug resistant pathogenic bacteria.