Affiliation:
1. Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire 03755
2. Bioinformatics Shared Resource, Dartmouth College, Hanover, New Hampshire 03755
Abstract
ABSTRACT
Enteric pathogens have developed several resistance mechanisms to survive the antimicrobial action of bile. We investigated the transcriptional profile of
Vibrio cholerae
O1 El Tor strain C6706 under virulence gene-inducing conditions in the presence and absence of bile. Microarray analysis revealed that the expression of 119 genes was affected by bile. The mRNA levels of genes encoding proteins involved in transport were increased in the presence of bile, whereas the mRNA levels of genes encoding proteins involved in pathogenesis and chemotaxis were decreased. This study identified genes encoding transcriptional regulators from the TetR family (
vexR
and
breR
) and multidrug efflux pumps from the resistance-nodulation-cell division superfamily (
vexB
and
vexD
[herein renamed
breB
]) that were induced in response to bile. Further analysis regarding
vexAB
and
breAB
expression in the presence of various antimicrobial compounds established that
vexAB
was induced in the presence of bile, sodium dodecyl sulfate, or novobiocin and that the induction of
breAB
was specific to bile. BreR is a direct repressor of the
breAB
promoter and is able to regulate its own expression, as demonstrated by transcriptional and electrophoretic mobility shift assays (EMSA). The expression of
breR
and
breAB
is induced in the presence of the bile salts cholate, deoxycholate, and chenodeoxycholate, and EMSA showed that deoxycholate is able to abolish the formation of BreR-P
breR
complexes. We propose that deoxycholate is able to interact with BreR and induce a conformational change that interferes with the DNA binding ability of BreR, resulting in
breAB
and
breR
expression. These results provide new insight into a transcriptional regulator and a transport system that likely play essential roles in the ability of
V. cholerae
to resist the action of bile in the host.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
54 articles.
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