Inhibitors of lipopolysaccharide biosynthesis impair the virulence potential of<i>Escherichia coli</i>

Abstract

Inhibition of 3-deoxy-manno-octulosonate cytidylytransferase (CMP-KDO transferase; EC 2.7.7.38) by 8-amino-2,6-anhydro-3,8-dideoxy-d-glycero-d-talo-octonic acid (NH2dKDO) halts the growth of Gram-negative bacteria by depriving the cells of the 3-deoxy-d-manno-2-octulosonate required for the biosynthesis of the core region of the lipopolysaccharide components of the outer membrane. Low levels of this inhibitor increase the vulnerability of Escherichia coli to hydrophobic antibiotics, detergents, the complement-mediated antibacterial activity of serum, phagocytosis, and enhance the rate at which bacteria are cleared from the mouse bloodstream.