Capsule and lipopolysaccharide - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 528

the cell surface, but it is not known whether the glycan is synthesized directly
on this phospholipid or if it is synthesized on another molecule before transfer
to the phospholipid ( Tzeng et al., 2005 ). Once the capsule is synthesized, it
is transported through the inner membrane by the ABC transporter (KpsMT)
(reviewed in Vimr and Steenbergen, 2009 ). The final steps of glycan translocation
are mediated by KpsE, a representative of the PCP-3 subfamily, and KpsD,
an OPX protein ( Cuthbertson et al., 2009 ). A multiprotein export complex
comprising KpsMTED is thought to span the cell envelope ( Rigg et al., 1998 ;
McNulty et al., 2006 ). Like the group 1 and 4 translocation export proteins,
they are conserved in all isolates possessing a group 2 or 3 capsule, indicat-
ing that they also do not recognize any particular glycan repeat-unit structure.
The genes encoding group 2 and 3 K antigens are located on the chromosome
near serA and these glycans can be found together with a wide range of O
serotypes, many formed by a Wzy-dependent system.
EVASION OF HOST CELL DEFENSES
Mammals have evolved with the pressure of bacteria, viruses, and fungi and so
have developed ways of dealing with microbial infections; the most extensive
defense machinery is the immune system. The human immune system consists
of two branches, innate and adaptive immunity, between which there is exten-
sive crosstalk. Innate immunity has developed as a first line of defense against
challenges not necessarily seen before to protect the body from pathogens. Toll-
like receptors (TLR) are the major effectors of innate immunity which recognize
conserved structures in pathogens called pathogen-associated molecular patterns
(PAMPs), somewhat of a misnomer, as they are found in non-pathogenic as well
as pathogenic microbes; in Gram-negative bacteria, these include LPS, CPS, fla-
gella, and nucleic acids. Binding of TLRs to their respective ligands activates a
signaling cascade, resulting in recruitment and activation of immune cells, which
can then eliminate the threat. In addition to the cellular receptors, there are also
soluble complement proteins found in serum, which can bind directly to bacte-
rial cell surfaces leading to opsonization, phagocytosis, and formation of the
membrane attack complex leading to lysis. LPS and CPS are important parts of
the arsenal of virulence factors used by bacteria to circumvent these processes.
Lipid A structure influences susceptibility to
polycationic peptides
Cationic antimicrobial peptides (CAMPs) are short peptides secreted by immune
and epithelial cells in response to bacterial products, like LPS, and other inflam-
matory signals (reviewed in Brown and Hancock, 2006 ). It is well established
that the structure of lipid A has a profound effect on the susceptibility of bacte-
ria to CAMPs and polycationic drugs such as polymyxin B. These compounds
typically exploit negatively charged phosphate residues on the diglucosamine