Affiliation:
1. University of Pittsburgh School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, Pennsylvania, USA
Abstract
ABSTRACT
Vibrio cholerae
is an aquatic organism and facultative human pathogen that colonizes the small intestine. In the small intestine,
V. cholerae
is exposed to a variety of antimicrobial compounds, including bile.
V. cholerae
resistance to bile is multifactorial and includes alterations in the membrane permeability barrier that are mediated by ToxR, a membrane-associated transcription factor. ToxR has also been shown to be required for activation of the LysR family transcription factor
leuO
in response to cyclic dipeptides. LeuO has been implicated in the regulation of multiple
V. cholerae
phenotypes, including biofilm production and virulence. In this study, we investigated the effects of bile on
leuO
expression. We show that
leuO
transcription increased in response to bile and bile salts but not in response to other detergents. The bile-dependent increase in
leuO
expression was dependent on ToxR, which was found to bind directly to the
leuO
promoter. The periplasmic domain of ToxR was required for basal
leuO
expression and for the bile-dependent induction of both
leuO
and
ompU
transcription.
V. cholerae
mutants that did not express
leuO
exhibited increased bile susceptibility, suggesting that LeuO contributes to bile resistance. Our collective results demonstrate that ToxR activates
leuO
expression in response to bile and that LeuO is a component of the ToxR-dependent responses that contribute to bile resistance.
IMPORTANCE
The success of
Vibrio cholerae
as a human pathogen is dependent upon its ability to rapidly adapt to changes in its growth environment. Growth in the human gastrointestinal tract requires the expression of genes that provide resistance to host antimicrobial compounds, including bile. In this work, we show for the first time that the LysR family regulator LeuO mediates responses in
V. cholerae
that contribute to bile resistance.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
35 articles.
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