Meningitis-associated Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 296

Given the plethora of E. coli serotypes, it is striking that E. coli strains pos-
sessing the K1 capsular polysaccharide are predominant (approximately 80%)
among isolates from neonatal E. coli meningitis ( Robbins et al., 1974 ; Gross
et al., 1982 ; Korhonen et al., 1985 ) and most of these K1 isolates are associated
with a limited number of O serotypes (e.g. O18, O7, O16, O1, O45), belonging
to phylogenetic group B2 and to a lesser extent, to group D ( Sarff et al., 1975 ;
Bingen et al., 1998 ; Johnson et al., 2001 ; Bonacorsi et al., 2003 ). The basis of
this association of phylogenetic groups B2 and D with E. coli meningitis has
not been elucidated.
The development of both in vitro and in vivo models of the blood-brain
barrier has facilitated our investigations on the mechanisms of the microbial
traversal of the blood-brain barrier, a key step required for the development
of E. coli meningitis ( Kim, 2001, 2002, 2003, 2008, 2010, 2012 ). The blood-
brain barrier protects the brain from microbes circulating in the blood, but
meningitis-causing pathogens have been shown to traverse the blood-brain bar-
rier transcellularly, paracellularly and/or by means of infected phagocytic cells
(Trojan-horse mechanism) ( Kim, 2008 ). Recent studies have demonstrated that
meningitis-causing E. coli K1 strains exhibit the ability to traverse the blood-
brain barrier by transcellular penetration and cause central nervous system
(CNS) inflammation, resulting in meningitis ( Kim, 2001, 2002, 2003, 2008,
2010, 2012 ) .
E. COLI TRAVERSAL OF THE BLOOD-BRAIN BARRIER
The blood-brain barrier is a structural and functional barrier that is formed by
brain microvascular endothelial cells (BMEC), astrocytes, and pericytes ( Rubin
and Staddon, 1999 ). It regulates the passage of molecules into and out of the
brain to maintain the neural microenvironment, and astrocytes and pericytes
help maintain the barrier property of BMEC. The contributions of astrocytes
and pericytes to E. coli traversal of the blood-brain barrier are, however, shown
to be minimal.
The in vitro blood-brain barrier model has been developed with human
brain microvascular endothelial cells (HBMEC). Upon cultivation on colla-
gen-coated Transwell inserts these HBMEC exhibit morphologic and func-
tional properties of tight junction formation and form a polarized monolayer.
These properties are shown by the demonstrations of tight junction proteins
(such as claudin 5 and ZO-1) and adherens junction proteins (such as VE-
cadherin and β-catenin) and their spatial separation, as well as development
of high transendothelial electrical resistance ( Stins et al., 1997, 2001 ; Kim
et al., 2004 ; Ruffer et al., 2004 ). Our previous studies with scanning and trans-
mission electron microscopy documented the internalization of meningitis-
causing E. coli K1 strains into HBMEC, as shown by the demonstration that
internalized bacteria are found within membrane-bound vacuoles of HBMEC
( Figure 10.1 ). E. coli K1 transmigrates the HBMEC monolayer through an