Lipopolysaccharide as a Target for the Development of Novel Therapeutics in Gram-Negative Bacteria

Lipopolysaccharide (LPS) constitutes the lipid portion of the outer leaflet of Gram-negative bacteria, and is essential for growth. LPS is also known to be responsible for the variety of biological effects associated with Gram-negative sepsis. In recent years, tremendous progress has been made in determining the exact chemical structure of this highly complex macromolecule, and recent advances have elucidated much of the enzymology involved in its biosynthesis. Using this knowledge, a number of inhibitors to LPS biosynthesis have been developed: some of these compounds have antibacterial properties, while others show excellent in vitro activity and are undergoing further investigation. This review summarizes the main features of LPS structure, function, and biosynthesis, highlighting the potential target reactions that have been or might be exploited for therapeutic intervention.