The Bile Response Repressor BreR Regulates Expression of the
            <i>Vibrio cholerae breAB</i>
            Efflux System Operon

Cerda-Maira, Francisca A.; Ringelberg, Carol S.; Taylor, Ronald K.

doi:10.1128/jb.00584-08

Cited by 54 publications

(64 citation statements)

References 53 publications

(81 reference statements)

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“…Ligand predictions based on phylogenomics are not limited to antibiotics. For example, BreR binds bile acids and is thought to be important to the survival of Vibrio cholerae in the intestinal tract (39). BreR and AefR share 30% identity (67% similarity) and grouped together in our analysis (Fig.…”

Section: Predicting Ligandsmentioning

confidence: 99%

The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

446

489

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SUMMARY The most common prokaryotic signal transduction mechanisms are the one-component systems in which a single polypeptide contains both a sensory domain and a DNA-binding domain. Among the >20 classes of one-component systems, the TetR family of regulators (TFRs) are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters. However, TFRs play a much broader role, controlling genes involved in metabolism, antibiotic production, quorum sensing, and many other aspects of prokaryotic physiology. There are several well-established model systems for understanding these important proteins, and structural studies have begun to unveil the mechanisms by which they bind DNA and recognize small-molecule ligands. The sequences for more than 200,000 TFRs are available in the public databases, and genomics studies are identifying their target genes. Three-dimensional structures have been solved for close to 200 TFRs. Comparison of these structures reveals a common overall architecture of nine conserved α helices. The most important open question concerning TFR biology is the nature and diversity of their ligands and how these relate to the biochemical processes under their control.

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Section: Predicting Ligandsmentioning

confidence: 99%

The TetR Family of Regulators

Cuthbertson

Nodwell

2013

Microbiol Mol Biol Rev

446

489

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“…Our laboratory has previously shown that the V. cholerae resistance-nodulation-division (RND) family efflux systems are major contributors to V. cholerae bile resistance (11)(12)(13)(14)(15). We therefore tested whether the contribution of leuO to bile resistance was mediated by upregulation of any of the RND efflux systems.…”

Section: Figmentioning

confidence: 99%

“…As such, enteric pathogens have evolved methods to overcome this barrier. This includes the modulation of outer membrane porin proteins to decrease the rate of diffusion of toxic molecules across the outer membrane and the expression of active efflux systems that remove bile salts from within the cell envelope (11)(12)(13)(14)(15). In V. cholerae, resistance to the antimicrobial effects of bile is due to the combined actions of multiple factors, including active efflux-and ToxR-regulated genes.…”

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confidence: 99%

Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance

et al. 2015

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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. IMPORTANCEThe 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. Vibrio cholerae is a Gram-negative bacterial pathogen and the causal agent of the severe diarrheal disease cholera. V. cholerae exists naturally in aquatic reservoirs and is capable of colonizing the human small intestine. The transition of V. cholerae from the aquatic ecosystem to growth in the human gastrointestinal tract is mediated by transcriptional responses that are required for colonization and disease development. Many of the genes that contribute to intestinal colonization are under the control of the membrane-associated regulatory protein ToxR, which functions as one of the primary regulators in the ToxR regulon (reviewed in reference 1). The ToxR regulon is divided into two branches, a ToxTdependent branch, which controls the expression of virulence factors, and a ToxT-independent branch, which reciprocally regulates the production of the outer membrane porins OmpU and OmpT. The ToxT-dependent branch of the ToxR regulon is a hierarchical regulatory cascade that regulates the expression of genes encoding the production of cholera toxin (CT) and the toxin-coregulated pilus (TCP) in response to environmental cues in the host.ToxR is a membrane-associated ...

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“…Bile salts are amphipathic molecules that act as detergents aiding in lipid solubilization and digestion but also play a role in host defense, as they have potent antimicrobial properties (26). For this reason, bile resistance is an essential characteristic of enteric bacteria and is achieved primarily via active efflux mechanisms (6,32,35,53,64) and altered permeability of the outer membrane (64,70). The RND efflux systems have been well described as playing a significant role in bile resistance among Gram-negative bacteria (45).…”

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confidence: 99%

Bile Salts Induce Resistance to Polymyxin in Enterohemorrhagic Escherichia coliO157:H7

et al. 2011

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Many enteric bacteria use bile as an environmental cue to signal resistance and virulence gene expression. Microarray analysis of enterohemorrhagic Escherichia coli O157:H7 (EHEC) treated with bile salts revealed upregulation of genes for an efflux system (acrAB), a two-component signal transduction system (basRS/ pmrAB), and lipid A modification (arnBCADTEF and ugd). Bile salt treatment of EHEC produced a basS-and arnT-dependent resistance to polymyxin.

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The Bile Response Repressor BreR Regulates Expression of the Vibrio cholerae breAB Efflux System Operon

Cited by 54 publications

References 53 publications

The TetR Family of Regulators

The TetR Family of Regulators

Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance

Bile Salts Induce Resistance to Polymyxin in Enterohemorrhagic Escherichia coliO157:H7

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