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Regulatory hierarchy of fimbrial expression
Regulation of type 1 fimbriae has been the focus of several studies, since this is one
of the major factors required for virulence in the murine model of ascending UTI.
The promoter of the type 1 fimbrial operon is located on an invertible sequence
(designated the
fim
switch) and causes type 1 fimbriae to be phase-variable. Phase
variation is dependent on the activity of two recombinases, FimB and FimE. FimB
can reverse the orientation of the
fim
switch from either the on-to-off or off-to-on
direction, whereas FimE primarily works only in the on-to-off direction. There-
fore, any regulation that changes the ratio of these recombinases or enhances or
suppresses their activity, will affect the proportion of
E. coli
expressing type 1 fim-
briae. P and S fimbriae can affect the expression of type 1 fimbriae via inhibition of
FimB activity, which then forces the
fim
switch into the off position from the action
of FimE (
Xia et al., 2000
;
Holden et al., 2001, 2006
). The negative regulation of
type 1 fimbrial expression by F1C, S and P fimbriae is due to regulatory proteins,
FocB, SfaB, or PapB, associated with the respective fimbrial operons (
Xia et al.,
2000
;
Holden et al., 2001
;
Lindberg et al., 2008
). Furthermore, P fimbriae posi-
tively regulate the expression of S fimbriae (
Morschhauser et al., 1994
), suggesting
that both fimbriae are utilized by the bacteria to colonize the same niche. When
taken together with the negative regulation of type 1 fimbriae, the hierarchy of
regulation begins to appear such that while type 1 fimbriae are needed for adher-
ence in an earlier niche, such as in the bladder, they may hinder adherence later,
such as in the kidneys, where P and S fimbriae are utilized. This type of hierarchi-
cal regulation could be essential for a pathogen like UPEC to ensure that only fim-
briae necessary for adherence to a particular substrate are expressed at any given
time, as well as to limit exposure of each antigen to the immune system, allowing
the pathogen to avoid clearance brought on by an antibody response. How the
uncharacterized fimbriae feed into this regulatory system remains to be elucidated.
Non-fimbrial adhesins
Factor adherence
E. coli
: FdeC
FdeC is an ExPEC adhesin that is found in 99% of ExPEC, 82.6% of commensal,
and 93-100% of intestinal pathogenic
E. coli
strains (
Nesta et al., 2012
). FdeC is
only expressed upon contact with host cells and has structural similarity to intimin
(from enteropathogenic
E. coli
) and invasin (from
Yersinia pseudotuberculosis
),
two bacterial virulence factors that mediate host cell interactions. Recombinant
FdeC binds epithelial cells and collagens V and VI (both present in the human
urinary tract) with high affinity and, in vivo,
E. coli
536 wild-type significantly
outcompetes a
fdeC
mutant in colonization of the bladder and kidneys (
Nesta
et al., 2012
). Thus, FdeC is a non-fimbrial adhesin necessary for full urovirulence.
RTX-like adhesin: TosA
TosA is a repeat-in-toxin (RTX) protein highly associated with UPEC (
Vigil
et al., 2011b
). Originally thought to encode a toxin due to sequence similarity
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