Carbohydrate Antigens
287
surveillance. Accordingly, such structural
mimicry poses a challenge to the devel-
opment of an effective vaccine to protect
against this infection. NMR and other
experiments found, however, that the cap-
sular polysaccharide of the bacteria can
adopt a unique ‘‘antigenic conformation’’
of helical structures, which are pathogen-
speciFc and are not cross-reactive with
the smaller oligomers of sialic acid ex-
pressed by human tissue. This led the way
to design and develop chemically mod-
iFed sugar chain vaccines, whereby the
pathogen-speciFc polymer helical struc-
tures were better preserved. In an im-
munization using one of the compounds,
N-propionylated group B meningococcal
polysaccharide (NPrGBMP),
the
major
population of antibodies elicited showed
no signiFcant cross-reactivity with
α
(2–8)-
polysialic acid, but preserved all bacte-
ricidal activity
in vitro
and protectivity
in vivo
.
2.3
Biological Complexity
By reviewing the chemical characteristics
of carbohydrates, it is clearly seen that
carbohydrate chains can have almost un-
limited variation. The actual variation in
carbohydrate structure in a given organ-
ism, is, however, restricted by the complex-
ity of biosynthesis of carbohydrates. Sugar
chains are not primary gene products. The
biosynthesis of a carbohydrate chain is
catalyzed step by step by a cluster of spe-
ciFc enzymes, called
glycosyltransferases
.
±or example, a cluster of genes directs the
biosynthesis of the group B
meningococci
capsular polysaccharide (GBMP) that we
discussed above. Each enzyme is responsi-
ble for a speciFc chemical reaction for the
synthesis of the molecule. Glycosyltrans-
ferases are protein products of genes. ±or
every new carbohydrate structure, a gene
must be provided. It is, thus, believed that
any given organism has a limited number
of variations in carbohydrates. Carbohy-
drates are, however, the most abundant
organic substances and are produced by
virtually all the living organisms. They may
employ various mechanisms and path-
ways for sugar chain synthesis. Thus, the
overall repertoires of diversity and com-
plexity of naturally occurring carbohydrate
molecules can be extraordinarily large.
Bacterial polysaccharides are typically
much more complex than those produced
by plants or animals. They are often par-
tially composed of unusual sugar residues
that are rarely seen in higher eukaryotic
species. Although only nine monosaccha-
rides are commonly seen in mammals,
over a hundred different monosaccha-
rides are found in bacteria. Some of
these sugars, such as ketodeoxyoctonic
acid, were previously thought to be lim-
ited in their occurrence to LPS. Other
interesting examples include the identi-
Fcation of hexosaminuronic acids in a
wide range of bacterial polymers, amino-
hexuronic acid in
E. coli K7
,
Streptococcus
pneumoniae
type 12 ± and
Achromobacter
georgipolitanum
; amphipathic exopolysac-
charide ‘‘emulsan’’ from
Acinetobacter cal-
coaceticus
; and the presence of several
o
-methyl sugars, including an
o
-methyl-
6-deoxyhexose, in the exopolysaccharide
sheath. In addition to carbohydrates, the
microbial polysaccharides contain vari-
ous ester-linked substituents and pyruvate
ketals, which are frequently of immuno-
logical signiFcance.
Glycoproteins are present in both mam-
mals and microbes. The prokaryotic mi-
croorganisms synthesize the N-linked and
the O-linked oligosaccharides on proteins,
just as mammals and other eukaryotes
do. Their glycosylation machineries have,
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