The Salmonella enterica Serovar Typhi LeuO Global Regulator Forms Tetramers: Residues Involved in Oligomerization, DNA Binding, and Transcriptional Regulation

Guadarrama, Carmen; Medrano-López, Abraham; Oropeza, Ricardo; Hernández-Lucas, Ismael; Calva, Edmundo

doi:10.1128/jb.01484-14

Cited by 22 publications

(22 citation statements)

References 59 publications

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“…2B, lane 2) and was further shifted with increasing concentrations of MBP-LeuO (lanes 4 and 5). It is unclear whether the additional shifting of the probe resulted from MBPLeuO multimerization, as has been reported with LeuO in Salmonella enterica serovar Typhi (41). Incubation of the carRS probe with MBP alone did not result in a mobility shift (lane 6), indicating that LeuO-MBP binding to the carRS promoter probe was due to LeuO and not due to nonspecific binding by the MBP.…”

Section: Resultsmentioning

confidence: 74%

Vibrio cholerae LeuO Links the ToxR Regulon to Expression of Lipid A Remodeling Genes

et al. 2016

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Vibrio cholerae is an intestinal pathogen that causes the diarrheal disease cholera. Colonization of the intestine depends upon the expression of genes that allow V. cholerae to overcome host barriers, including low pH, bile acids, and the innate immune system. ToxR is a major contributor to this process. ToxR is a membrane-spanning transcription factor that coordinates gene expression in response to environmental cues. In previous work we showed that ToxR upregulated leuO expression in response to bile salts. LeuO is a LysR family transcription factor that contributes to acid tolerance, bile resistance, and biofilm formation in V. cholerae. Here, we investigated the function of ToxR and LeuO in cationic antimicrobial peptide (CAMP) resistance. We report that ToxR and LeuO contribute to CAMP resistance by regulating carRS transcription. CarRS is a two-component regulatory system that positively regulates almEFG expression. AlmEFG confers CAMP resistance by glycinylation of lipid A. We found that the expression of carRS and almEFG and the polymyxin B MIC increased in mutants lacking toxRS or leuO. Conversely, leuO overexpression decreased the polymyxin B MIC. Furthermore, we found that LeuO directly bound to the carRS promoter and that ToxR-dependent activation of leuO transcription regulated carRS transcription in response to bile salts. Our results suggest that LeuO functions downstream of ToxR to modulate carRS expression in response to environmental cues. This study extends the functional role of ToxR and LeuO in environmental adaptation to include cell surface remodeling and CAMP resistance. Vibrio cholerae is a Gram-negative facultative human pathogen and the causative agent of the diarrheal disease cholera. V. cholerae is native to aquatic ecosystems, where it often associates with chitinous aquatic organisms (reviewed in reference 1). People acquire V. cholerae by ingestion of contaminated food or water. Following ingestion, V. cholerae colonizes the small intestine, where it produces virulence factors that result in a severe secretory diarrhea that is the hallmark of the disease cholera. The secretory diarrhea then contributes to V. cholerae transmission to new hosts and dissemination into the aquatic ecosystem.The ability of V. cholerae to rapidly transition between the aquatic ecosystem and the host is essential for its success as a pathogen. Colonization of the human gastrointestinal tract is mediated by transcriptional responses that facilitate adaptation to dynamic environments in the gastrointestinal tract. Following ingestion, V. cholerae activates the expression of virulence factors that are essential for both colonization and disease development. This includes the production of the enterotoxin cholera toxin (CT) and an adhesin called the toxin coregulated pilus (TCP) (2, 3). The expression of many V. cholerae virulence genes is coordinately regulated by the ToxR regulon (4). The ToxR regulon is divided into two branches: the ToxT-dependent branch and the ToxT-independent branch. In the ToxT-depe...

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Section: Resultsmentioning

confidence: 74%

Vibrio cholerae LeuO Links the ToxR Regulon to Expression of Lipid A Remodeling Genes

et al. 2016

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“…To support the critical role of flagellar motility in various stages of this bacterium's life cycle, a number of regulators (e.g., H-NS, Crp, Lrp, RcsB, LrhA) have been shown or implicated to influence the flhD upstream region (5,66,(89)(90)(91). Furthermore, it has recently been proposed that the Salmonella enterica global regulator LeuO binds to DNA differently to initiate or impede transcription of target genes (92). Distal as well as proximal binding profiles of MrpJ were evident for both the mrp gene and the flhD upstream regulatory element in vivo, suggesting that the binding of MrpJ on separate regions preceding its target genes occurs during both gene activation as well as repression.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

et al. 2015

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The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections (UTIs). Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for disease progression. Previously, the transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has been shown to repress both swimming and swarming motility. Here we show that MrpJ affects an array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking levels observed during UTIs leads to differential expression of 217 genes related to, among other functions, bacterial virulence, type VI secretion, and metabolism. We probed the molecular mechanism of transcriptional regulation by MrpJ using transcriptional reporters and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence-associated target gene promoters, the promoters of the flagellar master regulator flhDC and mrp itself, appears to be affected by the condensation state of the native chromosome, although both targets share a direct MrpJ binding site proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observed that mrpJ is widely conserved in a collection of recent clinical isolates. Altogether, these findings support a role of MrpJ as a global regulator of P. mirabilis virulence. Bacterial pathogens utilize a myriad of complex regulatory networks to adapt gene expression in response to environmental cues encountered in the host. Trying to walk a fine balance of avoiding detection by the host immune system, while ensuring acquisition of all essential nutrients and promoting growth, bacteria employ transcriptional and posttranscriptional strategies to combat the host's defenses. A prominent example is the specific induction of iron and zinc uptake systems during infection, regulated by Fur and Zur, respectively, which allows pathogens to gain access to these essential transition metals in the restricted host environment (1, 2).Urinary tract infections (UTIs) are among the most common bacterial infections (3), presenting a significant public health burden amounting to annual costs of about 3.5 billion dollars in the United States alone (4). Although Proteus mirabilis causes a relatively small proportion of UTIs in healthy individuals, it is a common cause of cystitis and pyelonephritis in individuals with indwelling catheters or anatomical abnormalities of the urinary tract (4, 5).UTIs occur almost exclusively in an ascending route, meaning that bacteria of fecal origin gain entry to the bladder via the urethra and then spread to the kidneys via the ureters (4). Initially, bacteria adhere to host epithelial cells via proteinaceous supramolecular structures referred to as fimbriae (or pili) (6), which allow pathogens to withstand the mechanical flow of urine (5)...

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“…Residue 303DG is not represented in the model of the LrhA effector binding domain. However, in case of the LysR-type regulator LeuO of S. enterica the C-terminal residues affect transcription activation by LeuO (Guadarrama et al, 2014).…”

Section: Screen For Hyperactive Lrha Mutantsmentioning

confidence: 99%

Activation of leuO by LrhA in Escherichia coli

Breddermann

Schnetz

2017

Molecular Microbiology

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LeuO is a conserved LysR-type transcription factor of pleiotropic function in Enterobacteria. Regulation of the leuO gene has been best studied in Escherichia coli and Salmonella enterica. Its expression is silenced by the nucleoid-associated proteins H-NS and StpA, autoregulated by LeuO, and in E. coli activated by the transcription regulator BglJ-RcsB. However, signals which induce leuO expression remain unknown. Here we show that LrhA, a conserved LysR-type transcription regulator, activates leuO in E. coli. LrhA specifically binds the leuO regulatory region and activates expression of leuO from three promoters. Activation of leuO by LrhA is synergistic with activation by BglJ-RcsB, while co-regulation by LrhA, LeuO and H-NS/StpA suggests a complex regulatory interplay. In addition, hyperactive LrhA mutants including LrhA-12DN, 221TA, 61HR/221TA and 303DG were identified. Regulation of leuO by LrhA reveals a connection between the two pleiotropic regulators LeuO and LrhA in E. coli.

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The Salmonella enterica Serovar Typhi LeuO Global Regulator Forms Tetramers: Residues Involved in Oligomerization, DNA Binding, and Transcriptional Regulation

Cited by 22 publications

References 59 publications

Vibrio cholerae LeuO Links the ToxR Regulon to Expression of Lipid A Remodeling Genes

Vibrio cholerae LeuO Links the ToxR Regulon to Expression of Lipid A Remodeling Genes

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

Activation of leuO by LrhA in Escherichia coli

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