Meningitis-associated Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 309

E. coli K1 + E. coli K1 -

EE
(EEA1, TfR)

LE
(Rab7, Lamp1)

Ly
(cathepsin D)

FIGURE 10.3 Intracellular trafficking of E. coli containing vacuoles in HBMEC monolayer. In
the absence of the K1 capsule (K1 - , right), the vacuoles mature to fuse with lysosomes and display
sequential markers of early endosome (EE), late endosome (LE) and lysosomes (Ly). By contrast,
the presence of the K1 capsule (K1 + , left) interferes with the vacuole maturation to prevent fusion
with lysosomes. This allows E. coli K1 to traverse HBMEC monolayer as live bacteria. EEA, early
endosomal antigen; TfR, transferring receptor; LAMP, lysosome-associated membrane protein.
(Adapted from Kim, 2003 , figure 3.)

E. coli K1 capsule is well recognized for its serum resistance and anti-
phagocytic properties ( Cross et al., 1986 ; Kim et al., 1986, 1988 ), which are the
essence of inducing a high degree of bacteremia. Another novel property of the
K1 capsule is, therefore, to modulate the maturation process of vacuoles con-
taining E. coli K1 encapsulated strain and prevent their fusion with lysosomes,
which is an event necessary for traversal of the blood-brain barrier as live bac-
teria. Additional studies are needed to understand how the K1 capsule is able
to modulate intracellular trafficking of E. coli K1-containing vacuoles to avoid
fusion with lysosomes in HBMEC and whether similar events occur with other
meningitis-causing microorganisms.

IDENTIFICATION OF MICROBIAL FACTORS INVOLVED IN
E. COLI MENINGITIS BY FUNCTIONAL GENOMIC APPROACHES
Genome sequencing of meningitis-causing microorganisms provides new tools
for elucidating the pathogenesis of meningitis. For example, comparative genome
analysis of the prototypic meningitis-causing E. coli K1 strain RS218 (O18:K1)
versus laboratory K-12 strain MG1655 identified 22 R S 218- d erived i islands
(RDIs) that are larger than 10 kb but are absent in strain MG1655 ( Xie et al.,
2006a,b ). The total length of these RDIs is approximately 793 kb, which replaced