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in LPS species, this system can effectively handle molecules with diverse struc-
tures and it is well conserved across bacterial species though it has been identified
only recently. In the current working model, LptBFG form an ABC protein com-
plex to extract nascent LPS out of the inner membrane. The molecule is passed via
LptC to a filament of LptA molecules spanning the periplasm and then to LptDE
located in the outer membrane, which completes translocation to the cell surface
(reviewed in Ruiz et al., 2009 ; Sperandeo et al., 2009 ; Chng et al., 2010 ).
Most LPS modifications occur at the periplasmic face of either the inner or
outer membrane and, as such, can serve as markers indicating the stage of trans-
port. These include modification of the phosphate groups with 4-amino-4-de-
oxy-L-arabinose (L-Ara4N) or ethanolamine by enzymes found in the inner
membrane, which increases bacterial resistance to innate immune defenses
(see below). The outer membrane protein PagP adds a secondary palmitate in
an acyloxyacyl linkage to the hydroxy-myristate located at the 2-position. The
resulting heptaacyl species is a much less potent activator of cytokine induc-
tion ( Raetz et al., 2007 ). PagP is normally latent in E. coli but is activated by
membrane perturbations and by defects in acylation of the 3ยด position of the
diglucosamine backbone with a myristol residue. However, this modification
can alter host-pathogen interactions in other ways, because PagP activity in
E. coli O157 has an indirect effect on the completion of the LPS core oligosac-
charide, leading to loss of O antigen and serum sensitivity ( Smith et al., 2008 ).
STRUCTURE AND BIOSYNTHESIS OF E. COLI CPSs
The CPSs of E. coli have been subdivided into four groups based on structural
and genetic criteria (reviewed in Whitfield, 2006 ). Group 1 and 4 capsules share
the same mode of synthesis, a Wzy-dependent pathway, and mainly differ in
the chromosomal locations of key genes. Similarly, groups 2 and 3 capsules
are both produced by ABC transporter-dependent processes but the genes are
organized differently within the locus.
Group 1 (and 4) CPS are found in E. coli isolates causing intestinal infec-
tions. They are heteropolymers of repeating sugar units, as in many O antigens.
Biosynthesis uses a process identical to the Wzy-dependent O antigens but the
pathways diverge once the polymerized glycan is formed at the periplasmic face
of the inner membrane ( Figure 17.4 ). O antigens enter the LPS assembly path-
way by ligation to lipid A-core and are transferred to the surface via Lpt proteins.
Capsular K antigens have their own surface assembly process that involves four
key components: (i) Wzc, an inner membrane PCP protein belonging to the PCP-
2a subfamily; (ii) Wzb, a cytoplasmic protein tyrosine phosphatase; (iii) Wza, an
outer membrane lipoprotein belonging to the OPX (outer membrane polysac-
charide export) protein family ( Cuthbertson et al., 2009 ); and (iv) an accessory
outer membrane protein called Wzi. Understanding the group 1 CPS transloca-
tion processes has come from studies with the serotype K30 prototype in the
Whitfield laboratory. In O-antigen biosynthesis, the corresponding PCP protein
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