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c
ytotoxic
n
ecrotizing
f
actor (
cnf-1
). J96 and 536 both encode yersiniabactin at
PAI-
asnT
, but 536 has three additional PAIs at
selC
,
leuX
, and
thrW
. In 536,
pap
and
hly
are located at PAI-
selC
, a second copy of
hly
and P-related fimbriae
genes (
prf
) are found at PAI-
lueX
, and
S
-type
f
imbrial
a
dhesion (
sfa
) and iron
siderphore (
iro
) genes are located at PAI-
thrW
. In addition to the PAI encoded
genes, CFT073 also has several potential virulence factors located outside of
PAIs (
Welch et al., 2002
). These include seven putative auto-transporters and 12
putative fimbriae (10 chaperone-usher and two type IV).
In 2006, two additional UPEC isolates were sequences. UTI89 was
sequenced by
Chen et al. (2006)
at Washington University. UTI189 was isolated
from the urine of a patient with cystitis and the genome consists of 5.1 Mbps
and one plasmid, pUTI89, which is 114 230 bps. There are 5066 predicted pro-
tein-coding genes and four large PAIs. In contrast,
Brzuszkiewicz et al. (2006)
sequenced UPEC strain 536, isolated from the urine of a patient with pyelone-
phritis. The 536 genome contains 4.9 Mbps, 4747 predicted coding sequences,
and no plasmids. Comparison of five
E. coli
genomes revealed 432 genes that
were present in UPEC strains 536 and CFT073 but not in EDL933, Sakai, or
laboratory strain K12 MG1655; this analysis suggested that these genes may
have a role in urovirulence. Additionally, 427 genes were identified that were
present in 536 but absent in all other published
E. coli
genomes (
Brzuszkiewicz
et al., 2006
). Many of these genes are found in PAIs. PAI-
selC
encodes
hyl
and
two sets of fimbriae genes; PAI-
leuX
contains another copy of
hyl
and
prf
; PAI-
thrW
contains
sfa
and
iro
genes; PAI-
asnT
contains yersiniabactin genes; and
PAI-
pheV
contains capsule genes. By creating PAI deletion mutants they found
PAI-
selC
, -
leuX
, and -
asnT
all contributed to virulence in a mouse model of
ascending UTI, while only deletion of PAI-
selC
and PAI-
leuX
together had an
impact on virulence in a mouse model of urosepsis. This result suggested that
there are many factors that contribute to UTI establishment, but
hly
, which is
found in two copies on PAI-
selC
and PAI-
leuX
is associated with the later stages
of urosepsis.
In 2007, Lloyd et al. described ten new genomic islands in CFT073, in addi-
tion to the three previously described PAIs, by comparative genome hybridiza-
tion of 10
E. coli
strains (
Lloyd et al., 2007
). In 2009, Lloyd et al. compared
nine genomic island mutants in a mouse model of ascending UTI. PAI-
metV
and PAI-
aspV
mutants were out-competed by wild-type CFT073 in the bladder
and genes c3405-c3409 of PAI-
metV
were found to be important for coloniza-
tion of both bladder and kidneys and specific to UPEC. PAI-aspV was further
dissected, and contact-dependent inhibition gene cdiA and the autotransporter
protease gene
picU
were determined to be important for colonization of the
bladder. The RTX family exoprotein A gene,
tosA
, was important for coloniza-
tion of the kidneys. PAI-aspV additionally contains a copy of the ferric binding
protein (
fbp
) operon, which is also present in genomic island cobU. Deletion of
both copies of the
fbp
operon was required for attenuation. This work empha-
sized that no single factor was responsible for virulence, even within a single
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