Meningitis-associated Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 298

TABLE 10.1 Mechanisms involved in E. coli traversal of the blood-brain barrier

Mechanisms E. coli factors Host factors

1. A high-degree of bacteremia K1, O-LPS, NlpI PMNs, complement

2. E. coli binding to HBMEC NlpI FimH, FliC, OmpA CD48, gp96,

3. E. coli invasion of HBMEC Ibe proteins, AslA, CNF1 37LRP

4. Traversal of the BBB as live
bacteria

K1 Rab7

A threshold level of bacteremia required for E. coli penetration
into the brain
Several studies in humans and experimental animals point to a relationship
between the magnitude of bacteremia and the development of meningitis due to
E . coli . For example, a significantly higher incidence of E. coli meningitis was
noted in neonates who had bacterial counts in blood higher than 10 3 colony-
forming units (CFU)/ml (6 out of 11 or 55%), compared to those with blood bac-
terial counts lower than 10 3 CFU/ml (1 out of 19 or 5%) ( Dietzman et al., 1974 ).
A high degree of bacteremia was also shown to be a primary determinant for
penetration into the brain by circulating E. coli K1 in neonatal and adult animals
with experimental hematogenous E. coli meningitis ( Kim et al., 1992 ; Huang
et al., 1995, 1999 ; Wang et al., 1999, 2004 ; Hoffman et al., 2000 ; Khan et al.,
2002 ; Wang and Kim, 2002 ), but an approximately 10 6 -fold greater inoculum of
E. coli K1 is required to induce a similar high-level bacteremia in adult animals
compared to neonatal animals ( Kim et al., 1992 ). These findings suggest that
the age dependency of E. coli meningitis is most likely due to the relative resis-
tance of adults to high-level bacteremia, which precedes the development of
meningitis, and less likely due to greater invasion of meningitis-causing E. coli
in HBMEC derived from neonates compared to those from adults. This concept
is shown by our demonstration that the abilities of meningitis-causing E. coli
K1 to bind and invade BMEC are similar between BMEC derived from young
and old rats as well as HBMEC derived from different ages ( Stins et al., 1999 ).
Thus, one of the reasons for the close association of meningitis-causing E. coli
strains with neonatal meningitis is their ability to escape from host defenses
and then to achieve a threshold level of bacteremia necessary for invasion of the
meninges. Taken together, these findings indicate that the prevention of bacte-
rial multiplication in the blood that is required for penetration into the brain
would be one potential approach for prevention of E. coli meningitis.
Previous studies have identified that the expression of K1 capsular polysac-
charide and O-lipopolysaccharide (LPS) are shown to be critical for induction