Uropathogenic Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 284

neutrophil infiltration of the urinary tract in response to UPEC can be delayed
by the secretion of SPATES.
Extracellular polysaccharides
In a signature tagged mutagenesis study of E. coli CFT073, mutation of genes
involved in biosynthesis of group II capsule and the enterobacterial common anti-
gen were attenuated in the mouse model of ascending UTI ( Bahrani-Mougeot et al.,
2002 ). Similarly, an isogenic mutant lacking the K2 capsule biosynthetic genes
was outcompeted by wild-type E. coli CFT073 in the mouse model of ascending
UTI ( Buckles et al., 2009 ). Furthermore, the K2 capsule was found to be necessary
for serum resistance ( Buckles et al., 2009 ). Recently, it has been suggested that
capsule polysaccharides are involved in the formation of intracellular biofilm-like
communities by some UPEC strains, as deletion of biosynthetic K capsule genes
reduced IBC formation in the mouse model of UTI due to infiltration of neutro-
phils ( Anderson et al., 2010 ). Again, the mechanism by which K capsule promotes
IBC formation has yet to be discovered. Several roles for capsular polysaccharides
in the avoidance of the host response to infection have been suggested, but as of
yet, none have been verified experimentally. Polysaccharides may reduce phago-
cytosis, opsonization, killing by antimicrobial peptides, and the formation of the
membrane attack complex ( Goller and Seed, 2010 ). Further studies are necessary
to fully understand the role polysaccharides play in vivo during UTI.
SulA and filamentation
SulA is an inhibitor of cell division that is activated by the SOS response to
DNA damage, such as that caused by the oxidative burst from PMNs ( Huisman
et al., 1980 ). The inhibition of cell division causes E. coli to take on a fila-
mentous morphology, which is thought to confer resistance to killing by PMNs
( Justice et al., 2004 ). In the cystitis strain E. coli UTI89, a sulA mutant is not able
to form filaments in vivo, suggesting that SulA is responsible for the filamen-
tous UPEC observed after fluxing from IBCs ( Justice et al., 2006a ). The sulA
mutant was attenuated in bladder colonization in the mouse model of ascending
UTI, but in tlr4 -/- knockout mice, the sulA mutant was not significantly different
in bladder colonization from the wild-type strain E. coli UTI89 suggesting that
filamentation is involved in evasion of the innate immune response to cystitis
( Justice et al., 2006a ). The mechanism by which filamentation aids the bacteria
to avoid the innate immune system has not been elucidated as of yet, but is
hypothesized to be due to decreased phagocytosis by PMNs.
Other virulence factors
Mutant strains of DegS ( Redford et al., 2003 ), DegP ( Redford and Welch,
2006 ), and PhoU ( Buckles et al., 2006 ), were attenuated in the mouse model of
infection, and complementation restored virulence. However, the role that these
proteins play in uropathogenesis is still unknown.