Uropathogenic Escherichia coli - Escherichia coli: Pathotypes and Principles of Pathogenesis - page 276

with other RTX proteins such as hemolysin, tosA was of interest to researchers
studying the pathogenesis of UPEC for two reasons. First, tosA is encoded on
a pathogenicity island that, when deleted, rendered E. coli CFT073 attenuated
in the mouse model of ascending UTI ( Lloyd et al., 2009a ).Upon deletion of
tosA itself, the deletion strain was outcompeted in vivo, demonstrating that the
attenuation of the PAI deletion strain was due, at least in part, to the deletion of
tosA ( Lloyd et al., 2009a ). Second, tosA was hit in an IVIAT screen, a method
for identification of antigenic proteins that are expressed only in vivo ( Vigil
et al., 2011a ). TosA is outer membrane-associated in E. coli , but does not have
a cytotoxic effect on mammalian cells ( Vigil et al., 2012 ). Rather, when over-
expressed, TosA increases adherence of E. coli CFT073 to kidney epithelial
cell lines, suggesting that TosA acts as an afimbrial adhesin mediating intimate
attachment to the upper urinary tract ( Vigil et al., 2012 ).
Autotransporters
Autotransporters are proteins that undergo type V secretion (Chapter 16), and
can either be secreted into the extracellular mileu or remain attached to the bac-
terial cell surface. Eleven autotransporter-encoding genes have been identified
in the uropathogenic E. coli strain CFT073 ( Parham et al., 2004 ; Allsopp et al.,
2010 ). Some, like Sat, are secreted toxins, but most autotransporters in UPEC
remain membrane-associated. Here we discuss the autotransporter proteins that
enhance adherence to uroepithelial cells or biofilm formation.
UpaG
UpaG is associated with E. coli phylogroups B2 and D, which include the uro-
pathogens ( Valle et al., 2008 ; Totsika et al., 2012 ). UpaG mediates adherence to
human bladder epithelial cells in vitro ( Valle et al., 2008 ; Totsika et al., 2012 )
and promotes cell aggregation, biofilm formation, and binding to the human
extracellular matrix proteins fibronectin and laminin ( Valle et al., 2008 ). How-
ever, when tested in the mouse model of ascending UTI, a upaG deletion mutant
had no fitness defect when compared to wild-type E. coli CFT073 ( Valle et al.,
2008 ), suggesting that the role of this protein during infection is too subtle to be
detected as a fitness defect.
UpaH
UpaH is highly prevalent in all E. coli strains tested, as it is found in 86% of A,
85% of B1, 84% of B2, and 70% of phylogenetic group D ( Allsopp et al., 2010 ).
However, in E. coli K-12 the pseudogene encoding UpaH, ydbA , is truncated by
insertion sequences ( Allsopp et al., 2010 ). In wild-type E. coli CFT073, UpaH
promotes biofilm formation on abiotic surfaces in M9 minimal medium. UpaH
is also expressed in vivo during infection and the upaH deletion strain was
significantly outcompeted by wild-type E. coli CFT073 in the mouse bladder,
demonstrating that this autotransporter adhesin is involved in uropathogenesis