Capsule and lipopolysaccharide - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 534

capsule has been shown to confer serum resistance in the absence of phagocytes
and also decreases the attachment and internalization of bacteria by PMNs and
monocytes ( Burns and Hull, 1999 ). The K1, K2, and K54 capsule antigens have
also been shown to be important for serum resistance in the absence of phago-
cytes ( Russo et al., 1993 ; Buckles et al., 2009 ). In the case of the K54 capsule, the
same amount of C3 was deposited on wild-type and capsule-minus strains, sug-
gesting that the capsule may prevent killing by complement rather than activation
of complement ( Russo et al., 1993 ).
O antigen is also important for serum resistance. Isogenic mutants lacking
the O antigen are extremely susceptible to killing by human serum containing
PMNs ( Burns and Hull, 1998 ). However, simple possession of the O antigen
is not always sufficient as the chain length of the O antigen is also important.
Studies with E. coli O-antigen biosynthesis mutants have shown that cells with
successively shorter O antigens are more susceptible to serum mediated killing
( Burns and Hull, 1998 ). E. coli Nissle 1917 is a well-known probiotic strain
which is not pathogenic due to a mutation in the wzy gene ( Grosdanov et al.,
2002 ). This mutation results in a lipid A-core which is capped with only one O
antigen repeat unit, rendering the cell sensitive to serum despite the presence of
a K5 capsule. In all cases, loss of both capsule and O antigen has a synergistic
effect on serum sensitivity ( Burns and Hull, 1998 ; Russo et al., 1995 ; Schneider
et al., 2004 ).
OTHER ROLES IN VIRULENCE
LT binds E. coli LPS
Heat-labile enterotoxin (LT) is a member of the AB 5 family of toxins and is
found in many ETEC isolates (for more details, see Chapter 6). All proteins
from this family, including cholera toxin (CT) and Shiga-like toxin, have the
same basic structure ( Beddoe et al., 2010 ). The A domain is an ADP-ribosylat-
ing enzyme which ultimately causes the efflux of water and electrolytes from
epithelial cells into the lumen of the intestine. The B domain consists of a pen-
tameric ring where each subunit binds a receptor on the epithelial cell surface.
Ganglioside GM 1 is the receptor for both LT and CT and the binding sites for the
ligand are found on one face of the ring, allowing for high avidity binding to the
epithelial cell surface ( Merritt et al., 1994 ). Both LT and CT are secreted from
the bacterial cell, but over 95% of LT remains associated with outer-membrane
vesicles through an interaction with LPS ( Horstman and Kuehn, 2002 ). This
association is mediated by a binding site on the B domain that is located on
the opposite side of the ring to the GM 1 -binding pocket ( Mudrak et al., 2009 ).
While LT may bind with higher affinity to full-length LPS, the minimum part of
the LPS required for binding has been shown to be the core Kdo residues ( Horst-
man et al., 2004 ). Interestingly, CT also binds to E. coli LPS but neither CT nor
LT bind to Vibrio LPS, perhaps because the Vibrio LPS core contains a single