Bordetella pertussis fim3 gene regulation by BvgA: Phosphorylation controls the formation of inactive vs. active transcription complexes

  title={Bordetella pertussis fim3 gene regulation by BvgA: Phosphorylation controls the formation of inactive vs. active transcription complexes},
  author={Alice Boulanger and Kyung Ho Moon and Kimberly Baxter Decker and Qing Ching Chen and Leslie Knipling and Scott E. Stibitz and Deborah M. Hinton},
  journal={Proceedings of the National Academy of Sciences},
  pages={E526 - E535}
Significance The response regulator BvgA controls virulence gene expression in the human pathogen Bordetella pertussis. Phosphorylated BvgA together with RNA polymerase form transcription complexes that synthesize RNA from the B. pertussis promoter for the fimbrial gene fim3. We show that nonphosphorylated BvgA and RNA polymerase form stable but inactive complexes. We propose that these complexes may modulate fim3 expression under inducing conditions and facilitate rapid repression of the fim3… Expand
The BvgAS Regulon of Bordetella pertussis
The first RNA-seq analysis of the BvgAS regulon in B. pertussis is reported, revealing that more than 550 genes are regulated by BVGAS and showing for the first time that genes for multiple and varied metabolic pathways are significantly upregulated in the B.pertussis Bvg(−) mode. Expand
Multiple weak interactions between BvgA~P and ptx promoter DNA strongly activate transcription of pertussis toxin genes in Bordetella pertussis
The weak/medium binding affinity of Pptx revealed in this study explains its lower responsiveness to phosphorylated BvgA, relative to other promoters containing a high affinity binding site, such as that of the fha operon. Expand
VpsR and cyclic di-GMP together drive transcription initiation to activate biofilm formation in Vibrio cholerae
The results suggest that c-di-GMP is required for VpsR to generate the specific protein–DNA architecture needed for activated transcription, a previously unrecognized role for c- DiGMP in gene expression. Expand
The BvgASR virulence regulon of Bordetella pertussis.
The BvgAS two-component system of Bordetella pertussis directly activates the expression of a large number of virulence genes in an environmentally responsive manner. The Bvg+ mode also promotes theExpand
VpsR Directly Activates Transcription of Multiple Biofilm Genes in Vibrio cholerae
Using biochemical methods, it is demonstrated for the first time that VpsR/c-di-GMP directly activates σ70-RNA polymerase at the first genes of the vps and ribomatrix operons, widening the mechanism of c-di.GMP-dependent transcription activation and the specific role of VPSR in biofilm formation. Expand
Compartment and signal-specific codependence in the transcriptional control of Salmonella periplasmic copper homeostasis
This work establishes that the coordinated interaction between a broad envelope stress transduction system and a signal-specific cytoplasmic sensor integrates a precise signal- and compartment-restricted output. Expand
Pertussis: Microbiology, Disease, Treatment, and Prevention
Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology, which provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines. Expand
Metal complexes promoting catalytic cleavage of nucleic acids-biochemical tools and therapeutics.
This review focuses on recent progress in the design and synthesis of metal complexes as artificial nucleases that promote either hydrolytic or oxidative cleavage of nucleic acids. Expand


The Bordetella pertussis model of exquisite gene control by the global transcription factor BvgA.
Two virulence genes, fim2 and fim3, which encode serologically distinct fimbrial subunits, are regulated using a previously unrecognized RNA polymerase/activator architecture, demonstrating one aspect whereby B. pertussis, which is highly clonal and lacks the extensive genetic diversity observed in many other bacterial pathogens, has been highly successful as an obligate human pathogen. Expand
Nature of DNA binding and RNA polymerase interaction of the Bordetella pertussis BvgA transcriptional activator at the fha promoter
DNA binding and in vitro transcription analyses were initiated to examine the activities of BvgA and RNA polymerase (RNAP) purified from both B. pertussis and Escherichia coli at the fha promoter and discovered that unphosphorylated BVGA binds to a single region (-100 to -70, relative to the start of transcription), whereas phosphorylatedBvgA binds both this region and another, farther downstream, that extends to the -35 nucleotide. Expand
In vivo phosphorylation dynamics of the Bordetella pertussis virulence‐controlling response regulator BvgA
The results provide the first direct evidence that levels of BVGA∼P in vivo correspond temporally to the expression of early and late BvgA‐regulated virulence genes, as well as a number of other aspects of Bvg a function predicted from previous studies and by analogy with other two‐component response regulators. Expand
Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation.
It is proposed that mutations affect transcription of the fim genes by varying the distance between the binding site for an activator and the −10 box, which is likely to be involved in both positive regulation by the bvg locus, and phase variation. Expand
Different requirements for σ Region 4 in BvgA activation of the Bordetella pertussis promoters P(fim3) and P(fhaB).
The results suggest that the -35 region of P(fim3) accommodates a BvgA~P dimer, an α subunit C-terminal domain, and σ Region 4, which suggests a novel mechanism of activation. Expand
Strong inhibition of fimbrial 3 subunit gene transcription by a novel downstream repressive element in Bordetella pertussis
The Bvg‐regulated promoters for the fimbrial subunit genes fim2 and fim3 of Bordetella pertussis behave differently from each other both in vivo and in vitro. In vivo Pfim2 is significantly strongerExpand
Transcription activation by the siderophore sensor Btr is mediated by ligand-dependent stimulation of promoter clearance
It is reported that Bacillus subtilis Btr, a member of the AraC family of activators, functions principally as a ligand-dependent activator of promoter clearance, while having only modest effects on either RNAP promoter association or the production of abortive transcripts. Expand
Novel architectural features of Bordetella pertussis fimbrial subunit promoters and their activation by the global virulence regulator BvgA
A prominent feature of the promoters of Bordetella pertussis fimbrial subunit genes fim2, fim3 and fimX is the presence of a ‘C‐stretch’, a monotonic run of C residues, and it is found that the three optimized promoters align perfectly. Expand
Activation of the global gene regulator PrrA (RegA) from Rhodobacter sphaeroides.
It is shown that treatment of PrrA with a phosphate analogue, BeF(3)(-), results in dimerization of the protein, producing a protein that binds DNA, suggesting that there is no direct blockage of DNA binding in the inactive state but rather thatPrrA dimerized promotes a correct arrangement of two adjacent DNA-binding domains that recognizes specific DNA binding sequences. Expand
Hybrid Bordetella pertussis-Escherichia coli RNA Polymerases: Selectivity of Promoter Activation
This work constructed hybrid Bordetella pertussis-Escherichia coli RNA polymerases and compared productive interactions between transcription activators and cognate RNA polymerase subunits in an in vitro transcription system to suggest that activator contact sites involve a high degree of selectivity. Expand