Activation of the
            <i>vrg6</i>
            Promoter of
            <i>Bordetella pertussis</i>
            by RisA

Cróinı́n, Tadhg Ó; Grippe, Vanessa K.; Merkel, Tod J.

doi:10.1128/jb.187.5.1648-1658.2005

Cited by 19 publications

(28 citation statements)

References 38 publications

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“…Genetic studies to date have indicated that vrg regulation involves at least two genes, bvgR and risA, which have negative and positive effects, respectively, on vrg expression (21,26,27). This indicates a different regulatory mechanism from that of the Bvg-activated genes (vag genes), which are controlled directly by the BvgAS TCS.…”

Section: Discussionmentioning

confidence: 95%

“…Due to the previous finding that RisA is an activator of vrg expression in B. pertussis (26,27), and our demonstration here that RisA is phosphorylated in vivo, we investigated whether RisA phosphorylation is required for vrg expression. To understand the role of RisA phosphorylation in the activation of vrg genes, pQC1304, containing the BRP-1304-lux fusion described above, was introduced into various B. pertussis strains.…”

Section: Resultsmentioning

confidence: 99%

“…Given the sequence similarity of RisAS to other TCS in the conserved RR and HK domains and additionally to OmpR and EnvZ in their DNA-binding and periplasmic domains, respectively, we hypothesized that RisA is phosphorylated as part of its role as an activator of vrg genes in B. pertussis (25,26). To determine if RisA is phosphorylated in vivo in B. pertussis, we tested cultures of wild-type (WT) B. pertussis strain BP536 or derivatives thereof after growth on BG agar for 2 days at 37°C.…”

Section: Resultsmentioning

confidence: 99%

“…Its gene is present in an operon together with that for an EnvZ-related HK, risS. Both genes have homologues in B. pertussis, and subsequent work revealed that the B. pertussis risA gene (open reading frame [ORF] BP3554) is required for expression of at least one vrg, vrg6 (26). While the risS gene is intact in B. bronchiseptica, B. pertussis strains uniformly harbor a risS gene inactivated by a frameshift mutation and therefore predicted to encode a truncated RisS (RisS=) protein (Fig.…”

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confidence: 99%

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Activation of Bvg-Repressed Genes in Bordetella pertussis by RisA Requires Cross Talk from Noncooperonic Histidine Kinase RisK

Chen

Warfel

et al. 2017

J Bacteriol

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The two-component response regulator RisA, encoded by open reading frame BP3554 in the Bordetella pertussis Tohama I genomic sequence, is a known activator of vrg genes, a set of genes whose expression is increased under the same environmental conditions (known as modulation) that result in repression of the bvgAS virulence regulon. Here we demonstrate that RisA is phosphorylated in vivo and that RisA phosphorylation is required for activation of vrg genes. An adjacent histidine kinase gene, risS, is truncated by frameshift mutation in B. pertussis but not in Bordetella bronchiseptica or Bordetella parapertussis. Neither deletion of risS= or bvgAS nor phenotypic modulation with MgSO 4 affected levels of phosphorylated RisA (RisAϳP) in B. pertussis. However, RisA phosphorylation did require the histidine kinase encoded by BP3223, here named RisK (cognate histidine kinase of RisA). RisK was also required for expression of the vrg genes. This requirement could be obviated by the introduction of the phosphorylation-mimicking RisA D60E mutant, indicating that an active conformation of RisA, but not phosphorylation per se, is crucial for vrg activation. Interestingly, expression of vrg genes is still modulated by MgSO 4 in cells harboring the RisA D60E mutation, suggesting that the activated RisA senses additional signals to control vrg expression in response to environmental stimuli. IMPORTANCE In B. pertussis, the BvgAS two-component system activates the expression of virulence genes by binding of BvgAϳP to their promoters. Expression of the reciprocally regulated vrg genes requires RisA and is also repressed by the Bvgactivated BvgR. RisA is an OmpR-like response regulator, but RisA phosphorylation was not expected because the gene for its presumed, cooperonic, histidine kinase is inactivated by mutation. In this study, we demonstrate phosphorylation of RisA in vivo by a noncooperonic histidine kinase. We also show that RisA phosphorylation is necessary but not sufficient for vrg activation but, importantly, is not affected by BvgAS status. Instead, we propose that vrg expression is controlled by BvgAS through its regulation of BvgR, a cyclic di-GMP (c-di-GMP) phosphodiesterase.KEYWORDS Bordetella pertussis, global virulence regulation, two-component regulatory systems, in vivo phosphorylation, transcriptional activation, Bvg-repressed gene, BvgAS, c-di-GMP B acteria widely employ two-component sensory transduction systems (TCSs) to sense environmental stimuli and mediate an adaptive response thereto. A typical TCS comprises a transmembrane sensor histidine kinase (HK), which undergoes autophosphorylation of its cytoplasmic domains upon sensing signals via its extracytoplasmic domain(s), and a cognate cytoplasmic response regulator (RR). The RR can accept phosphate from its cognate autophosphorylated HK and typically undergoes a conformational change leading to transcriptional activation of specific genes that correspond

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Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Activation of Bvg-Repressed Genes in Bordetella pertussis by RisA Requires Cross Talk from Noncooperonic Histidine Kinase RisK

Chen

Warfel

et al. 2017

J Bacteriol

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“…RisAS has been suggested to be required specifically for intracellular survival of the bacteria during infection (33). Interestingly, the genes in the RisAS regulon, whose expression appears to be required for intracellular survival and which are activated by Ris, are also part of the BvgAS regulon, but their expression is repressed by Bvg (14,61). This might suggest that these two systems control gene expression in response to different environments encountered during the infectious process (perhaps intracellular versus extracellular environments); however, a common theme is that each system must ensure the appropriate timing and levels of expression of the genes contained within its regulon and that failure to do so results in an attenuation of virulence for the organism (10,12,33).…”

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confidence: 99%

A Novel Sensor Kinase Is Required for Bordetella bronchiseptica To Colonize the Lower Respiratory Tract

Kaut¹,

Duncan

Kim³

et al. 2011

Infect Immun

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Bacterial virulence is influenced by the activity of two-component regulator systems (TCSs), which consist of membrane-bound sensor kinases that allow bacteria to sense the external environment and cytoplasmic, DNA-binding response regulator proteins that control appropriate gene expression. Respiratory pathogens of the Bordetella genus require the well-studied TCS BvgAS to control the expression of many genes required for colonization of the mammalian respiratory tract. Here we describe the identification of a novel gene in Bordetella bronchiseptica, plrS, the product of which shares sequence homology to several NtrY-family sensor kinases and is required for B. bronchiseptica to colonize and persist in the lower, but not upper, respiratory tract in rats and mice. The plrS gene is located immediately 5 to and presumably cotranscribed with a gene encoding a putative response regulator, supporting the idea that PlrS and the product of the downstream gene may compose a TCS. Consistent with this hypothesis, the PlrS-dependent colonization phenotype requires a conserved histidine that serves as the site of autophosphorylation in other sensor kinases, and in strains lacking plrS, the production and/or cellular localization of several immune-recognized proteins is altered in comparison to that in the wild-type strain. Because plrS is required for colonization and persistence only in the lower respiratory tract, a site where innate and adaptive immune mechanisms actively target infectious agents, we hypothesize that its role may be to allow Bordetella to resist the host immune response.

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The BvgASR virulence regulon of Bordetella pertussis

Chen

Stibitz

2019

Current Opinion in Microbiology

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Activation of the vrg6 Promoter of Bordetella pertussis by RisA

Cited by 19 publications

References 38 publications

Activation of Bvg-Repressed Genes in Bordetella pertussis by RisA Requires Cross Talk from Noncooperonic Histidine Kinase RisK

Activation of Bvg-Repressed Genes in Bordetella pertussis by RisA Requires Cross Talk from Noncooperonic Histidine Kinase RisK

A Novel Sensor Kinase Is Required for Bordetella bronchiseptica To Colonize the Lower Respiratory Tract

The BvgASR virulence regulon of Bordetella pertussis

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