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of a high degree of bacteremia (
Cross et al., 1986
;
Kim et al., 1986, 1988
), but
the feasibility of using the K1 capsule and O-LPS for the prevention of
E. coli
bacteremia has been shown to be limited (
Soderstrom et al., 1984
;
Finne et al.,
1987
;
Cross et al., 1994
).
Recent functional
E. coli
genomic studies identified several
E. coli
factors
that are shown to contribute to bacteremia (
Kim, 2008
;
Xie et al., 2008
;
Moriel
et al., 2010
). For example, NlpI is a lipoprotein located in the outer membrane
and has been shown to contribute to a high-level
E. coli
K1 bacteremeia. NlpI's
evasion of serum-mediated killing is through regulation of complement regula-
tor C4bp deposition on the bacterial surface (
Tseng et al., 2012
). Studies are
in progress to determine the protective and broadly conserved antigens or to
develop a multi-epitope subunit vaccine for the prevention of
E. coli
bacteremia
and subsequent meningitis (
Moriel et al., 2010
;
Wieser et al., 2012
).
E. coli
binding to and invasion of HBMEC
Subsequent studies have shown that a high degree of bacteremia is necessary,
but not sufficient for
E. coli
penetration of the blood-brain barrier in vivo, and
that
E. coli
binding to and invasion of HBMEC is a prerequisite for penetration
into the brain (
Huang et al., 1995, 1999
;
Wang et al., 1999
;
Hoffman et al.,
2000
;
Khan et al., 2002
;
Wang and Kim, 2002
), the essential step for the devel-
opment of
E. coli
meningitis. This was shown by the demonstration in infant
rats with experimental hematogenous meningitis that several isogenic mutants
of meningitis-causing
E. coli
K1 strain RS218 deleted of factors contributing
to HBMEC binding (e.g. OmpA) and invasion (e.g. Ibe proteins, CNF1) were
significantly less able to induce meningitis than the parent strain despite similar
levels of bacteremia (
Table 10.2
). These findings indicate that those
E. coli
fac-
tors contributing to HBMEC binding and invasion are necessary for crossing the
blood-brain barrier in vivo.
E. coli
factors contributing to HBMEC binding
Infections caused by pathogenic
E. coli
are often initiated by binding of the
bacteria to the host cell surface, and this concept is likely to be important for
circulating
E. coli
to withstand the blood flow in vivo and cross the blood-
brain barrier. Several
E. coli
factors are identified to be involved in binding to
HBMEC that subsequently affect invasion into HBMEC. These bacterial fac-
tors include type 1 fimbriae (FimH), flagella (FliC), outer membrane protein
A (OmpA) and a lipoprotein (NlpI) (
Khan et al., 2003, 2007
;
Shin et al., 2005
;
Teng et al., 2005, 2010
;
Parthasarathy et al., 2007
). The roles of these
E. coli
factors in HBMEC binding were verified by deletion and complementation
experiments. For example, isogenic deletion mutants were significantly less
able to bind HBMEC and their binding ability was restored to the level of the
parent strain by complementation with respective wild-type genes.
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