Affiliation:
1. Department of Microbiology, Roy J. and Lucille A. Carver School of Medicine, University of Iowa, Iowa City, Iowa
Abstract
ABSTRACT
An important step in
Salmonella enterica
serovar Typhimurium virulence is the ability to invade the intestinal epithelium. The invasion process requires a large number of genes encoded on
Salmonella
pathogenicity island 1 (SPI-1) at centisome 63 as well as genes located in other positions throughout the chromosome. Expression of the invasive phenotype is tightly regulated by environmental cues that are processed by a complex regulatory scheme. A central player in the invasion regulatory pathway is the HilA protein, which is transcriptional activator belonging to the OmpR/ToxR family. A number of positive regulators (
hilC
,
hilD
,
fis
,
sirA
/
barA
,
csrAB
,
phoBR
,
fadD
,
envZ
/
ompR
, and
fliZ
) and negative regulators (
hha
,
hilE
,
lon
,
ams
,
phoP
c
and
pag
) have been identified that are able to alter expression of
hilA
transcription. Recent work has found that
hilA
transcription requires the HilD protein for activation. Other work has emphasized the importance of HilE as a negative regulator of
hilA
. Overexpression of
hilE
superrepresses
hilA
transcription, as well as the invasive phenotype. Two-hybrid experiments suggest that HilE exerts its regulatory influence on
hilA
through protein-protein interactions with HilD as the protein does not bind to the
hilA
promoter nor does it affect
hilD
transcription. As it seems likely that
hilE
plays an important role in translating environmental signals into invasion gene regulation, we have attempted to identify how the
hilE
gene itself is regulated. Our results indicate that the
fimYZ
genes, response regulatory proteins involved in type 1 fimbrial gene expression and recently implicated in motility gene regulation, are important activators of
hilE
expression. These findings indicate that invasion gene expression is coregulated with motility and adherence and provide experimental evidence that the expression of these virulence phenotypes is a subset of the overall regulation of bacterial physiology.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference56 articles.
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Salmonella enterica
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