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IBCs, while mostly studied in the context of murine bladder infections, were
found in 22% of exfoliated epithelial cell samples from human UTIs (
Rosen
et al., 2007
). However, whether IBCs play a role in pathogenesis still needs to
be elucidated.
Iron acquisition
To survive in the human urinary tract, UPEC have evolved mechanisms to scav-
enge iron from the host. The human body utilizes heme, lactoferrin, transferrin,
and lipocalin-2 to sequester iron because this element, while essential for life, is
also toxic in high quantities. UPEC, therefore, use iron-chelating siderophores
to rip iron away from host iron-bound proteins, and also evolved mechanisms to
use the iron in heme itself. UPEC strains can synthesize up to four siderophores:
the hydoxamateaerobactin, two catecholates: enterobactin and salmochelin, and
yersiniabactin, a mixed-type siderophore. Each iron-bound siderophore is rec-
ognized by a cognate iron receptor: IroN mediates salmochelin uptake (
Russo
et al., 2002
), IutA mediates aerobactin uptake (
Torres et al., 2001
), Iha mediates
enterobactin uptake (
Johnson et al., 2005a, b
), and FyuA mediates yersinia-
bactin uptake (
Heesemann et al., 1993
;
Schubert et al., 2002
). ChuA and Hma
mediate direct heme uptake (
Torres et al., 2001
;
Hagan and Mobley, 2009
).
All of the iron acquisition systems are TonB-dependent, and demonstrating the
importance of iron scavenging in UTI, a
tonB
mutant is attenuated in the murine
model of ascending UTI (
Torres et al., 2001
). Complementation of the mutation
by expression of
tonB
from a vector restored virulence, thereby fulfilling Koch's
molecular postulates (
Torres et al., 2001
). While iron acquisition is necessary for
UPEC to cause infections, there is redundancy in the iron acquisition systems,
as no one siderophore-receptor system is essential for UTI. However, there is
a functional hierarchy during urinary tract colonization, in which enterobactin
and salmochelin receptors contribute the least and the heme and noncatecholate
siderophore receptors contribute the most to iron acquisition during infection
(
Garcia et al., 2011
).
Host response to UPEC, pathogen avoidance of host responses
Mechanical host response
The luminal surface of the bladder is made up of superficial umbrella cells
which are coated by uroplakins to which the type 1 fimbriae or UPEC bind (
Wu
et al., 2009
). This triggers exfoliation of the bladder epithelium (
Zhou et al.,
2001
). The shed uroepithelial cells, along with any adherent or intracellular bac-
teria, are then flushed out of the urinary tract by the flow of urine. Furthermore,
a protein present in high amounts in human urine, known as uromodulin, binds
type 1 fimbriae, thereby titrating UPEC away from receptors on the uroepithe-
lium (
Serafini-Cessi et al., 2003
).
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