Meningitis-associated Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 301

OFF mutant resulted in decreased invasion into HBMEC ( Teng et al., 2005 ;
Khan et al., 2007 ).
From our E. coli DNA microarray experiments, we identified a novel site-
specific recombinase, HbiF, which inverted the molecular switch fimS indepen-
dent of the two known recombinases, FimB and FimE, that invert fimS and
control the expression of the downstream fim operon ( Xie et al., 2006a,b ).
Discovery of HbiF-mediated fimS switching provides a new opportunity for
regulating type 1 fimbriae expression, which will help in developing a novel
strategy for the prevention and therapy of E. coli bacteremia and meningitis.
We also identified that FimH interacts with a glycosylphosphatidylinositol-
anchored receptor, CD48 on the surface of HBMEC, and FimH-CD48 inter-
action contributes to E. coli binding to HBMEC and increases in intracellular
Ca 2+ ([Ca 2+ ]i) in HBMEC ( Khan et al., 2007 ; Kim et al., 2008 ). This concept is
shown by the demonstration that CD48 antibody blocks FimH-mediated binding
to HBMEC and FimH-induced [Ca2+]i 2+ ]i changes in HBMEC ( Table 10.3 ).
S fimbriae, which bind to terminal NeuAc α2,3-galactose sequences pres-
ent on glycoproteins, have been implicated in E. coli binding to HBMEC. For
example, purified S fimbriae or a recombinant E. coli strain HB101 express-
ing S fimbriae was shown to bind to the luminal surfaces of the brain vascular
endothelium in neonatal rat brain tissues ( Parkkinen et al., 1988 ). We have pre-
viously shown using S fimbriated transformants of E. coli strain HB101 that S
fimbriae allowed this laboratory strain of E. coli to bind to HBMEC ( Prasadarao
et al., 1993 ; Stins et al., 1994 ), suggesting that S fimbriae contribute to E. coli
binding to HBMEC. However, in-frame deletion of the S fimbriae operon in

TABLE 10.3 Blood-brain barrier receptors used by E. coli and other
CNS-infecting microorganisms

Receptor Organism and ligand References

Gp96 Khan et al., 2003

E. coli OmpA

L. monocytogenes Vip Cabanes et al., 2005

37LRP E. coli CNF1 Chung et al., 2003

Orihuela et al., 2009

N. meningitidis PilQ/PorA

S. pneumoniae CbpA Orihuela et al., 2009

H. influenza type b Omp2 Orihuela et al., 2009

Prion protein Gauczynski et al., 2001

Viruses (sindbis, dengue, tick-borne
encephalitis, Venezuelan equine
encephalitis, adeno-associated)

Wang et al., 1992
Ludwig et al., 1996
Thepparit and Smith, 2004
Akache et al., 2006