Capsule and lipopolysaccharide - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 521

FIGURE 17.2 Structure of lipid A-core. (A) Structure of Kdo 2 -lipid A. (B) Structure of the R1 and
R3 core types. All linkages are in the alpha anomeric configuration unless otherwise noted. Dotted
lines represent non-stochiometric modifications. The site of O antigen attachment is indicated.
though this can be modified in several places to alter the biological properties
of the molecule (reviewed in Raetz et al., 2007 ) (see below). The core oligosac-
charide can be divided into two regions. The inner core consists of two residues
of 3-deoxy-D- manno -oct-2-ulosonic acid (Kdo) and three residues of L-glycero-
D- manno -heptose (Hep) but it may also be modified with a number of other
groups such as phosphate, pyrophosphorylethanolamine, or additional sugars
( Figure 17.2 B). This region is highly conserved in E. coli and Salmonella and
is important for membrane stability (reviewed in Heinrichs et al., 1998 ). For
example, loss of the phosphate moieties on Hep residues compromises outer
membrane integrity and, in Salmonella , attenuates virulence ( Yethon et al.,
2000 ). The outer core serves as the point of attachment for O-PS and con-
tains sugars such as glucose (Glc), galactose (Gal), glucosamine (GlcN), and
N-acetylglucosamine (GlcNAc). Despite the potential for great diversity, there
are only five known core types in E. coli , K-12, R1, R2, R3, and R4 ( Heinrichs
et al., 1998 ; Kaniuk et al., 2004 ). The core type R1 is most commonly found in
E. coli causing extraintestinal infection while the verotoxin-producing E. coli
isolates are predominantly R3 ( Figure 17.2 B).
Lipid A-core is synthesized as one unit in a step-wise manner by the Lpx
and Waa enzymes, starting with the acylation of UDP-GlcNAc on the cyto-
plasmic face of the inner membrane ( Figure 17.3 ) (reviewed in Raetz and
Whitfield, 2002 ; Raetz et al., 2007 ). Most of the steps in this process were