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the adhesiveness of PMNs to epithelial cells, impairing the transmigration of
PMNs and eliciting an oxidative burst that contributes to epithelial cell dam-
age characteristic of UTI ( Hofman et al., 2000 ). Furthermore, phagocytosis by
PMNs is also inhibited by CNF-1, again impeding clearance of UTI by the
innate immune system ( Hofman et al., 2000 ). In a mouse model of ascending
UTI CNF-1-positive strains induced higher levels of inflammation and colo-
nized the urine and bladders better than cnf-1 isogenic mutants ( Rippere-Lampe
et al., 2001 ). However, another study showed the opposite, which could be due
to differences in the mouse strain studied, or the type of UPEC isolates charac-
terized ( Johnson et al., 2000 ). In the study that showed no defect in colonization
by a cnf-1 isogenic mutant, the E. coli strain was isolated from a patient with
cystitis. The strains in which the cnf-1 mutant had an effect were isolated from
the blood of a patient with urosepsis. A third hypothesis for the discrepancy in
the results is that the strain used in the study by Johnson et al. might not produce
CNF-1. It was never tested for the ability to actually produce the toxin. There-
fore, more data are necessary before a generalized conclusion can be made as to
whether CNF-1 plays a role in vivo during UTI. However, the evidence supports
the hypothesis that CNF-1, when produced, can effectively inhibit the innate
immune system response to UPEC.
Serine protease autotransporters of Enterobacteriaceae
Uropathogenic E. coli encode three serine protease autotransporters (SPATES),
secreted by the type V mechanism (Chapter 16), and designated Sat, Pic, and
Tsh. All three SPATES are more prevalent in UPEC than fecal E. coli isolates:
sat is present in 68% of pyelonephritis isolates compared to 14% of fecal isolates
( Guyer et al., 2000 ), pic is present in 31% of pyelonephritis isolates compared
to 7% of fecal E. coli isolates,and tsh is present in 63% of all UPEC strains and
only 33% of fecal E. coli strains ( Heimer et al., 2004 ). Sat is expressed during
UTI in the mouse model of infection, and has a cytopathic effect on kidney
and bladder epithelial cells ( Guyer et al., 2000 ). While there is no significant
difference in colonization between a Sat-deficient mutant and wild-type in the
mouse model of ascending UTI, histological changes were apparent in the kid-
neys ( Guyer et al., 2002 ). Specifically, vacuolation of proximal tubule cells and
dissolution of the glomerular membrane was observed, indicating that Sat is a
vacuolating cytotoxin ( Guyer et al., 2002 ). Further study demonstrated Sat was
taken up by host cells and interacts with the cytoskeleton, causing actin loss and
cytoskeletal contraction within intoxicated cells ( Maroncle et al., 2006 ).
In E. coli CFT073, both pic and tsh are temperature-regulated, with higher
expression at 37°C. Bacteria from the urine of infected mice also express both
SPATES ( Heimer et al., 2004 ). Both Pic and Tsh cleave surface glycoproteins
from leukocytes, including CD43, PSGL-1, CD44, CD45, CD93, and fractal-
kine/CX3CL1 ( Ruiz-Perez et al., 2011 ). All targets of Pic and Tsh are involved
in leukocyte attraction and migration ( Ruiz-Perez et al., 2011 ). Thus, the
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