Chemistry Reference
In-Depth Information
17.1.2.1
B ab A and S ab A
The adhesins BabA and SabA mediate colonization of
H. pylori
to stomach epithe-
lial cells by binding to Lewis
b
( Le
b
) and sialyl - Lewis
x
( sLe
x
), respectively (Table
17.1). The former carbohydrate epitope is naturally expressed on secretor and
Lewis-positive individuals, whereas expression of the latter epitope seems to be
induced by
H. pylori
infection. It has been shown that BabA exists as allelic vari-
ants, of which some, generalists, recognize Le
b
- related structures such as
H type 1 and ALe
b
, while others are pure specialists, binding only to Le
b
. Approxi-
mately 50% of the world population is infected by
H. pylori
and 10% of these
develop peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lym-
phoma or gastric cancer.
17.1.2.2
L ec A and L ec B
Formerly known as PA-IL and PA-IIL, LecA and LecB [6] are unusual bacterial
lectins in the sense that they require the presence of Ca
2+
for carbohydrate binding,
which is a feature characteristic for several mammalian lectins (see Chapter 16.3
and Figure 16.1h,i,k,l; for details on C-type lectins, see Chapters 19 and 20). LecA
binds strongly to human P1 and p
k
blood group antigens as well as blood group
B, that is, terminal Gal
1,3Gal structures. LecB has an unusually
high affi nity for fucose, but also recognizes
L
- galactose,
D
- mannose and
D
- arabi-
nose which display the same stereochemical arrangement with one axial and two
vicinal equatorial hydroxyl groups. Lewis
a
( Le
a
) is very well recognized by LecB,
while the different orientation of the GlcNAc
N
- acetyl group of Le
x
is presumably
responsible for its considerably weaker binding to LecB. These lectins also have a
toxic function causing damage of epithelial cell primary cultures and blockage of
epithelial cell ciliary beating. The two lectins are expressed by
P. aeruginosa
- a
pathogen causing serious health problems in patients with cystic fi brosis, pneu-
monia, cancer or injured corneas. Some of these patients may have a changed
cell-surface glycosylation with increased fucosylation and decreased sialylation that
appears to promote
P. aeruginosa
binding.
α
1,4Gal and Gal
α
17.1.3
Toxins
Lectins presented on fi mbriae/pili or on the cell surface can directly mediate adhe-
sion of a bacterium to the host cell surface and facilitate host infection. Another
type of bacterial carbohydrate-binding proteins is constituted by secreted toxins,
which are of importance for bacterial pathogenicity.
17.1.3.1
Toxin A of
Clostridium d iffi cile
Toxin A is a 308-kDa protein with seven putative binding sites for
Gal
1,4GlcNAc (Table 17.1), presumably carried on both lipid and protein
carriers. The binding pocket may tolerate some modifi cations, such as fucosylation,
as binding to Le
x
and Lewis
y
( Le
y
) structures (please see Table 27.2 ) is also possible.
Upon binding to the host cell surface, toxin A is endocytosed. It glucosylates Rho
α
1,3Gal
β
