Characterization of Enhancer Binding by the
            <i>Vibrio cholerae</i>
            Flagellar Regulatory Protein FlrC

Correa, Nidia; Klose, Karl E.

doi:10.1128/jb.187.9.3158-3170.2005

Cited by 29 publications

(37 citation statements)

References 41 publications

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“…A reasonably good consensus 54 binding site was found located Ϫ112 to Ϫ97 with respect to the initiating methionine codon. This sequence (GGGTATAAATTTTGCT; Ϫ24 and Ϫ12 elements are underlined) maintains the invariant GG and GC elements with 10-bp spacing in between and shows an identical Ϫ12 sequence with two previously characterized FlrC-dependent promoters (6). Our data demonstrate that the VC2207-VC2206 operon is positively regulated by FlrC.…”

Section: Resultssupporting

confidence: 49%

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Lipidation of an FlrC-Dependent Protein Is Required for Enhanced Intestinal Colonization by Vibrio cholerae

et al. 2008

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Vibrio cholerae is a gram-negative bacterium responsible for the human disease cholera. V. cholerae is acquired by the consumption of contaminated food or water. Within the intestine, the bacteria express the toxin-coregulated pilus (TCP), which is essential for colonization of the intestinal epithelial cells (45). V. cholerae also expresses cholera toxin (CT), which leads to the copious amounts of watery diarrhea characteristic of a cholera infection (10).V. cholerae synthesizes a sheathed polar flagellum, and motility has been linked to virulence. Studies have demonstrated that nonmotile mutants are defective for fluid accumulation and adherence in the rabbit ileal loop model (37, 40) and adherence to isolated rabbit brush borders (11); nonmotile mutants are also defective for virulence in the rabbit RITARD (removable intestinal tie adult rabbit diarrhea) model (37). Nonmotile mutants of O1 El Tor biotype strains show colonization defects in the infant mouse model (25), while nonmotile classical biotype mutants generally colonize similarly to the motile wild-type strain (14). Nonmotile mutants of live V. cholerae vaccine strains show reduced reactogenicity (disease symptoms) in human volunteers while still being able to colonize the intestine (8, 19), demonstrating a role for motility in virulence in the natural human host.Though a number of studies have implicated motility as being important for V. cholerae virulence, the exact connection between flagellar synthesis and cholera pathogenesis is still not clear. In a study involving spontaneous mutants, Gardel and Mekalanos found that nonmotile mutants showed increased expression of CT and TCP while hypermotile mutants produced less CT and TCP than the wild-type V. cholerae, and they proposed a model where virulence and motility are inversely related (14). Recently, Silva et al. provided evidence for this model when they found that transcription of the genes encoding CT and TCP is upregulated in a V. cholerae nonmotile strain (40).The flagellum is a complex structure made up of multiple structural subunits, and the assembly of this structure is exquisitely coordinated in a stepwise fashion, initiating inside the cell and building outward toward the flagellar tip (29). The expression of flagellar genes is also tightly regulated, and V. cholerae has a four-tiered flagellar transcription hierarchy (36). There is a single class I gene, and it encodes the master regulator of the flagellar transcriptional hierarchy, FlrA. FlrA is a 54 -dependent transcriptional activator that activates the expression of class II genes, which encode primarily the MS ring and export apparatus components, as well as chemotaxis and regulatory factors, including FlrC (36). FlrC is a 54 -dependent transcriptional activator that is phosphorylated and activates class III flagellar genes (7), which encode the basal body and hook, as well as some of the switch and export apparatus components and the FlaA flagellin. FliA is an alternate sigma factor ( 28 ) that activates class IV genes, which e...

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Section: Resultssupporting

confidence: 49%

“…1B, FliA). This pattern of expression is characteristic of class III (FlrC dependent) promoters (6,36). A reasonably good consensus 54 binding site was found located Ϫ112 to Ϫ97 with respect to the initiating methionine codon.…”

Section: Resultsmentioning

confidence: 88%

Lipidation of an FlrC-Dependent Protein Is Required for Enhanced Intestinal Colonization by Vibrio cholerae

et al. 2008

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“…FlrB undergoes autophosphorylation, and then activates FlrC activity by transferring a phosphate to the conserved aspartate-54 (D54) residue in the amino terminus of FlrC (FlrC-P) allowing it to activate the σ 54 -dependent transcription of Class III genes (Correa, Lauriano et al 2000;Correa and Klose 2005). The class III genes encode the rest of the components of the hook-basal body, as well as the flagellin FlaA and the OM proteins FlgOP.…”

Section: Fig 3 Flagellar Transcription Regulatory Hierarchymentioning

confidence: 99%

“…One mechanism for achieving these different levels of expression is the relative binding strength of the FlrC sites, which bind FlrC strongly at the flaA promoter, but only weakly at other Class III promoters, e.g. the flgK promoter (Correa and Klose 2005).…”

Section: Fig 3 Flagellar Transcription Regulatory Hierarchymentioning

confidence: 99%

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Vibrio cholerae Flagellar Synthesis and Virulence

Anastasia¹,

Karl²

2012

Cholera

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The N‐terminal FleQ domain of the Vibrio cholerae flagellar master regulator FlrA plays pivotal structural roles in stabilizing its active state

et al. 2023

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In Vibrio cholerae, the master regulator FlrA controls transcription of downstream flagellar genes in a σ54‐dependent manner. However, the molecular basis of regulation by VcFlrA, which contains a phosphorylation‐deficient N‐terminal FleQ domain, has remained elusive. Our studies on VcFlrA, four of its constructs, and a mutant showed that the AAA+ domain of VcFlrA, with or without the linker ‘L’, remains in ATPase‐deficient monomeric states. By contrast, the FleQ domain plays a pivotal role in promoting higher‐order functional oligomers, providing the required conformation to ‘L’ for ATP/cyclic di‐GMP (c‐di‐GMP) binding. The crystal structure of VcFlrA‐FleQ at 2.0 Å suggests that distinct structural features of VcFlrA‐FleQ presumably assist in inter‐domain packing. VcFlrA at a high concentration forms ATPase‐efficient oligomers when the intracellular c‐di‐GMP level is low. Conversely, excess c‐di‐GMP locks VcFlrA in a non‐functional lower oligomeric state, causing repression of flagellar biosynthesis.

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Characterization of Enhancer Binding by the Vibrio cholerae Flagellar Regulatory Protein FlrC

Cited by 29 publications

References 41 publications

Lipidation of an FlrC-Dependent Protein Is Required for Enhanced Intestinal Colonization by Vibrio cholerae

Lipidation of an FlrC-Dependent Protein Is Required for Enhanced Intestinal Colonization by Vibrio cholerae

Vibrio cholerae Flagellar Synthesis and Virulence

The N‐terminal FleQ domain of the Vibrio cholerae flagellar master regulator FlrA plays pivotal structural roles in stabilizing its active state

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