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pyrophosphate, or it could potentially be released by a leaky polymerization
step, where the transfer of the growing chain to the incoming repeat unit may
be incomplete. Wzi is important for surface retention of group 1 CPS although
its precise function is not yet known and it is not present in group 4 systems
(
Rahn et al., 2003
). The Wza-Wzb-Wzc proteins are highly conserved in all iso-
lates possessing a group 1 or 4 capsule, indicating that they do not recognize
any particular glycan repeat-unit structure. Group 1 K antigens are typically co-
expressed with an O antigen synthesized by the ABC transporter pathway (e.g.
O8/O9/O9a) and the corresponding gene clusters are both located near
his
. The
group 1 gene cluster is allelic with genes for colanic acid biosynthesis, so expres-
sion of a capsule and colanic acid are mutually exclusive. However, group 4 K
antigens really emphasize the parallels between O- and K-antigen biosynthesis.
In these cases, the structures of the repeat units are identical and are produced by
the same chromosomal locus. Some undecaprenyl pyrophosphate-linked mol-
ecules are diverted by WaaL into LPS, while others enter a CPS translocation
pathway by Wza-Wzb-Wzc proteins that are encoded by a separated locus else-
where on the chromosome (
Peleg et al., 2005
). Serotype O111 provided the first
example, and the use of the same repeat structure led to the early description of
'
O-antigen capsules
' (now group 4) (
Goldman et al., 1982
). It is now known that
serotypes O127 and O157 also have group 4 capsules (
Table 17.1
) (
Peleg et al.,
2005
;
Shifrin et al., 2008
). Isolates that can produce group 4 CPSs (unlike their
group 1 counterparts) retain the genes for colanic acid production.
K antigens from extraintestinal pathogenic
E. coli
mostly fall into groups
2 and 3 (
Whitfield, 2006
). These include capsules from isolates causing
urinary tract infections and meningitis. The production of many of these
K antigens is temperature-regulated, unlike group 1 and 4 K antigens, with
expression being 'on' at 37°C but 'off' at temperatures below 20°C. Some
of the CPS structures resemble eukaryotic glycans and this is thought to aid
virulence by preventing an effective immune response. For example, the K4
glycan is fructosylated chondroitin and the K5 glycan is heparosan, both
similar to human glycosaminoglycans (
Table 17.1
). As well, the meningitis-
causing K1 isolates possess a CPS containing α2,8-linked polysialic acid,
which is identical in structure to the glycan found on neural cell adhesion
molecule (NCAM) in the human brain. The K1 and K5 systems have been
influential models for understanding the mechanisms of biosynthesis through
studies in the laboratories of Eric Vimr, Willie Vann, and Ian Roberts. ABC
transporter-dependent capsules are synthesized entirely on the cytoplasmic
face of the inner membrane, similar to ABC transporter-dependent O antigens
(
Figure 17.4
) (
Whitfield, 2006
). However, one critical difference is that unde-
caprenyl phosphate is apparently not involved (
Finke et al., 1991
). It has
been shown that the mature capsular polysaccharide is attached at the reduc-
ing end to a phospholipid although the precise chemical structure has not
been resolved (
Gotschlich et al., 1981
). In the essentially identical process in
N. meningitidis
, lipidation occurs before transport of polysialic acid CPS to
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