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structure (i.e. not only at the tip); and afimbrial adhesins such as autotrans-
porters. Extensive regulatory systems coordinate expression of these different
adhesins ( Snyder et al., 2005 ). Study of the regulatory networks coordinating
expression of fimbrial adhesins is an active area of research, which could even-
tually lead to the development of novel therapeutic targets.
Fimbriae
The prototypical pyelonephritis strain E. coli CFT073 encodes 12 fimbrial
operons in its genome ( Welch et al., 2002 ) including 10 chaperone-usher
fimbriae (Chapter 12) and two putative type IV pili (Chapter 13). Eight of the
chaperone-usher fimbriae have been studied for effects on uropathogenesis:
type 1, F1C, Auf, Ygi, Yad, F9, and two P fimbriae. The remaining four, Yeh;
Yfc; and two type IV pili, remain to be studied. Pix fimbriae have been asso-
ciated with uropathogenic E. coli and have been studied in the pyelonephitis
isolate E. coli 536, however, molecular epidemiologic data demonstrate that this
fimbria is rare ( Spurbeck et al., 2011 ). Dr fimbriae are fibrillar structures that have
been associated with uropathogenic strains of E. coli as well as diffuse adhering
E. coli (DAEC), and will be discussed below.
Type 1 fimbriae
Type 1 fimbriae, encoded in the genomes of most (99%) E. coli strains ( Vigil
et al., 2011a, b ), are necessary for colonization of the oropharynx as a precur-
sor to intestinal colonization ( Orndorff and Bloch, 1990 ). Type 1 fimbriae
primarily consist of FimA, the main structural subunit, several minor sub-
units, and the adhesin, FimH, which is found at the tip of the fimbriae as well
as intermittently throughout the shaft ( Klemm et al., 1990 ; Krogfelt et al.,
1990 ). These fimbriae enhance pathogenicity in the urinary tract by mediat-
ing adherence to and invasion of bladder epithelial cells by binding man-
nose moieties ( Brinton, 1959 ) and uroplakin 1a with the tip adhesin FimH
( Zhou et al., 2001 ), as well as by binding to muscle cells and vascular walls
( Virkola et al., 1988 ). Type 1 fimbriae cause damage to the urinary tract by
increasing inflammation during infection ( Connell et al., 1996 ). The promoter
for type 1 fimbriae resides within an invertible element (designated the fim
switch or fimS ), and thus type 1 fimbriae are subject to phase variation at the
level of transcription. This phase variation is regulated by the activity of two
recombinases, FimB and FimE, on the fim switch (see below in the section on
the regulation hierarchy of fimbriae). Type 1 fimbriae are a virulence factor
of UPEC in experimental models, as shown in the studies by Connell et al.
(1996) that demonstrated deletion of fimH reduced colonization and inflam-
mation in the mouse model of ascending UTI. Furthermore, colonization of
the murine urinary tract and inflammatogenicity were restored in the fimH
mutant by expression of fimH from a plasmid, fulfilling Koch's postulates
( Connell et al., 1996 ).
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