Affiliation:
1. Department of Microbiology, University of Iowa School of Medicine, Iowa City, Iowa 52242
Abstract
ABSTRACT
An early step in the establishment of
Salmonella enterica
serovar Typhimurium murine infection is the penetration of the intestinal mucosa of the small intestine. The majority of the genes responsible for the
Salmonella
invasive phenotype are encoded on
Salmonella
pathogenicity island 1, and their transcription is controlled by the
hilA
transcriptional activator. The expression of
hilA
is regulated by environmental signals including oxygen, osmolarity, pH, and growth phase such that the presence of any one suboptimal condition results in repression of
hilA
expression and the invasive phenotype. We have conducted a search for negative regulators of
hilA
by introduction of a
Salmonella enterica
serovar Typhimurium chromosomal DNA gene bank into a
Salmonella enterica
serovar Typhimurium
hilA
::Tn
5lacZY
reporter strain. This screen has identified the
hha
gene as a regulator that exerts a negative influence on
hilA
expression. Plasmid-encoded
hha
significantly reduces
hilA
::Tn
5lacZY
chromosomal expression, as well as expression of the invasion genes
invF
,
prgH
, and
sipC
. An
hha
null mutation results in substantial derepression of both chromosomally encoded and plasmid-encoded
hilA
::Tn
5lacZY
expression. Introduction of plasmid-encoded
hha
into strain SL1344 results in attenuation of invasion using in vitro and in vivo assays. Importantly, purified Hha protein was found to bind to a
hilA
DNA promoter fragment, suggesting that the regulatory activity of the Hha protein occurs at the
hilA
promoter. These data add detail to the developing model of the regulation of
Salmonella
invasion genes.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
72 articles.
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