Epithelial mucins and bacterial adhesion - Carbohydrate Chemistry: Chemical and Biological Approaches - page 612

5.2 Pseudomonas and Burkholderia lectins
The most serious complications in CF are respiratory tract infections by
the opportunistic pathogen Pseudomonas aeruginosa. In addition to the
inherent antibiotic resistance, the formation of biofilms in human lung
by this bacterium further complicates the treatment of chronic Pseudo-
monas infections. LecA and LecB are soluble lectins, both involved in
biofilm formation and regulated by quorum sensing. They contribute to
the pathogenicity of P. aeruginosa by facilitating self-self adhesion,
adhesion to mucosal surfaces, stimulation of inflammation and by sev-
eral cytotoxic effects on respiratory epithelial cells.
LecA (also called PA-IL) is a tetrameric cytotoxic lectin with specificity
for a- D -galactose and binding preferentially to a-Galp-(1 - 4)-b-Galp-

(1 4)-Glcp containing globotriaosylceramide sphingolipid. Figure 3

demonstrates the crystal structure of LecA in complex with iG b3 (a-Galp-
(1

-

O)-Cer) and the structural basis of the
anity for galactose by a calcium ion that bridges between the O3 and O4
of galactose (Fig. 3). 108,109
The crystal structure of the P. aeruginosa fucose-specific lectin LecB
(also called PA-IIL) revealed a tetramer of b-sandwiches with micromolar
anity for a- L -fucose and a moderate anity for a- D -mannose. 110 LecB is
particular because it has two bridging calcium ions in the fucose-binding
pocket, that serially link the hydroxyl groups on positions 2, 3 and 4 of
the L-fucose. LecB was solved in its metal-bound and metal-free states, in
complex with L -fucose, D -mannose and L -fructopyranose. All three
monosaccharides bound isosterically via direct interactions with two
bridging calcium ions as well as via direct hydrogen bonds with several
side chains. A putative C-terminal secretion motif was discovered

- 3)-b-Galp-(1 - 4)-b-Glcp-(1 -

O3

O3 O2

O4 O4

(a) (b)

Fig. 3 Crystal structure of Pseudomonas aeruginosa LecA and LecB soluble lectins. (a)
The crystal structure of LecA shown in complex with isoG b3 . 108 (b) The crystal structure of
LecB in complex with Le a . 110