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most of these K1 isolates are associated with a limited number of O sero-
types (e.g. O18, O7, O16, O1, O45), belonging to phylogenetic group B2 and
to a lesser extent, to group D ( Sarff et al., 1975 ; Korhonen et al., 1985 ;
Bonacorsi et al., 2003 ; Yao et al., 2006 ). The basis of their association with
E. coli meningitis, however, remains unclear. We have shown that arachi-
donic acid metabolism pathways contribute to meningitis-causing E. coli K1
strains of phlyogenetic groups B2 and D for their invasion of HBMEC and
penetration specifically into the brain ( Zhu et al., 2010a ). This was shown
by the demonstration that gene deletion and pharmacological inhibition of
arachidonic acid metabolism pathways prevent E. coli penetration specifi-
cally into the brain without affecting the level of bacteremia and penetration
into non-brain organs (e.g. kidney, spleen, and lung). These findings suggest
that determination of the microbial-host factors contributing to arachidonic
acid metabolism pathways leading to penetration of the blood-brain barrier
is likely to elucidate the novel concept of neurotropism in E. coli meningitis
and also provide the information on novel targets for prevention and therapy
of E. coli meningitis.
THE MECHANISMS INVOLVED IN CNS INFLAMMATION IN
RESPONSE TO BACTERIAL MENINGITIS
Bacterial meningitis is characterized by inflammation of the meninges that
occurs in response to bacteria and bacterial products, resulting in release of
cytokines and chemokines as well as pathophysiological alterations such as
infiltration of leukocytes and blood-brain barrier dysfunction ( Kim, 2003 ).
Recent studies have shown that the mechanisms involved in microbial invasion
of the blood-brain barrier differ from those involved in the release of cyto-
kines and chemokines in response to meningitis-causing pathogens ( Kim, 2008,
2010, 2012 ). For example, interleukin-8 secretion in response to E. coli strain
K1 happens in HBMEC, but not in non-brain endothelial cells (e.g. human
umbilical vein endothelial cells). However, E. coli factors involved in bind-
ing to and invasion of HBMEC did not affect the release of interleukin 8 from
HBMEC ( Galanakis et al., 2006 ). Similar findings were demonstrated for group
B Streptococcus and N. meningitidis ( Sokolova et al., 2004 ; Banerjee et al.,
2011 ). These findings suggest that targets for prevention of bacterial penetration
into the brain are likely to differ from those involved in CNS inflammation
associated with bacterial meningitis.
NEURONAL INJURY FOLLOWING E. COLI MENINGITIS
Neurological sequelae are common in survivors of neonatal E. coli meningitis,
but the underlying mechanisms remain incompletely understood ( Kim, 2003 ).
Neuronal injury stemming from cortical necrosis and hippocampal apopto-
sis is considered a major contributing factor. Experimental animal studies
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