Capsule and lipopolysaccharide - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 536

urethra to the bladder, attachment to the bladder wall, invasion and intracellular
bacterial community (IBC) formation, followed in more invasive cases by pos-
sible translocation to the blood to cause sepsis, or migration through the ureters
to the kidneys (see Chapter 9). Most of the UPEC isolates produce group 2 K
antigens ( Schneider et al., 2004 ) and a number of different group 2 capsules
have been shown to be important for UTI pathogenesis at different points in the
infection ( Johnson, 1991 ; Schneider et al., 2004 ; Snyder et al., 2004 ; Buckles
et al., 2009 ; Anderson et al., 2010 ). For example, the K1 capsule has also been
shown to contribute to the decreased IBC formation and resistance of those
IBCs to neutrophil penetration ( Anderson et al., 2010 ). There are more effectors
of complement in the kidneys compared to the bladder, and certain capsules and
O antigens confer protection to UPEC strains from complement, especially in
upper UTI infections ( Buckles et al., 2009 ).
Polysialic acid CPSs and meningitis
Meningitis is characterized by extreme inflammation of the meninges and
subarachnoid space caused by release of proinflammatory cytokines in
response to bacteria in the cerebrospinal fluid. This causes increased perme-
ability of the blood-brain barrier (BBB) and influx of fluid and leukocytes
which promote the inflammatory state. After group B Streptococcus , E. coli
K1 is the most common cause of neonatal meningitis in the developed world
( Gaschignard et al., 2011 ; Stoll et al., 2011 ). The E. coli K1 capsule consists
of polysialic acid and the same glycan is also found in the human brain, where
it contributes to the anti-adhesive properties of the neural cell adhesion mole-
cule (NCAM). Because it is normally found in human tissues, it is considered
non-immunogenic.
The transit of E. coli K1 to the cerebrospinal fluid is a multistep process
(see Chapter 10) involving translocation of the bacteria from the gut to the
blood, survival and multiplication in the bloodstream, followed by transloca-
tion of the bacteria through the BBB, all of which require the presence of
the polysialic acid capsule ( Kim et al., 1992 ; Mushtaq et al., 2004, 2005 ;
Xie et al., 2004 ). In the bloodstream, the K1 capsule prevents phagocytosis
and complement-mediated killing, as described above, allowing bacteremia
to occur. High levels of bacteremia are correlated with an increase in develop-
ment of meningitis ( Xie et al., 2004 ). Once a threshold is reached, the bacte-
ria can bind to brain microvascular endothelial cells (BMEC) where they are
internalized into endosomes which traverse the cell and release the bacteria
into the choroid plexus of the brain, where cerebrospinal fluid is produced.
The polysialic acid capsule has actually been shown to decrease the ability of
the bacteria to bind BMECs but once inside the BMECs, endosomes contain-
ing unencapsulated E. coli fuse with lysosomes. Only endosomes containing
encapsulated bacteria traverse BMECs and are released into the cerebro-
spinal fluid ( Kim et al., 2003 ). Once the bacteria are in the choroid plexus,