Affiliation:
1. Department of Microbiology & Immunology
2. Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109
Abstract
ABSTRACT
Extraintestinal pathogenic
Escherichia coli
can successfully colonize the urinary tract of the immunocompetent host. In part, this is accomplished by dampening the host immune response. Indeed, the
sisA
and
sisB
genes (
shiA
-like
i
nflammation
s
uppressor genes
A
and
B
) of uropathogenic
E. coli
strain CFT073, homologs of the
Shigella flexneri
SHI-2 pathogenicity island gene
shiA
, suppress the host inflammatory response. A double deletion mutant (Δ
sisA
Δ
sisB
) resulted in a hyperinflammatory phenotype in an experimental model of ascending urinary tract infection. The Δ
sisA
Δ
sisB
mutant not only caused significantly more inflammatory foci in the kidneys of CBA/J mice (
P
= 0.0399), but these lesions were also histologically more severe (
P
= 0.0477) than lesions observed in mice infected with wild-type CFT073. This hyperinflammatory phenotype could be suppressed to wild-type levels by in vivo complementation of the Δ
sisA
Δ
sisB
mutant with either the
sisA
or
sisB
gene in
trans
. The Δ
sisA
Δ
sisB
mutant was outcompeted by wild-type CFT073 during cochallenge infection in the bladder (
P
= 0.0295) at 48 h postinoculation (hpi). However, during cochallenge infections, we reasoned that wild-type CFT073 could partially complement the Δ
sisA
Δ
sisB
mutant. Consistent with this, the most significant colonization defect of the Δ
sisA
Δ
sisB
mutant in vivo was observed during independent challenge relative to wild-type CFT073, with attenuation of the mutant observed in the bladder (
P
< 0.0001) and kidneys (
P
= 0.0003) at 6 hpi. By 24 and 48 hpi, the Δ
sisA
Δ
sisB
mutant was no longer significantly attenuated in the bladder or kidneys, suggesting that the
sisA
and
sisB
genes may be important for suppressing the host immune response during the initial stages of infection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
42 articles.
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