Signal Transduction by BvgS Sensor Kinase

Dupré, Elian; Lesne, E.; Guérin, Jean-Dominique; Lensink, Marc F.; Verger, Alexis; Ruyck, Jérôme de; Brysbaert, Guillaume; Vezin, Hervé; Locht, Camille; Antoine, Rudy; Jacob‐Dubuisson, Françoise

doi:10.1074/jbc.m115.655720

Cited by 19 publications

(16 citation statements)

References 48 publications

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“…Transcription of bvgR is activated directly by BvgA~P binding to the promoter PbvgR (18). Somewhat atypically compared to other twocomponent sensor kinases, BvgS appears to be turned on, i.e., actively phosphorylating BvgA, in the absence of specific signals, with recent elegant biochemical, structural, and genetic studies supporting this view (19)(20)(21)(22)(23)(24)(25). However, BvgS can be turned off by addition of compounds such as MgSO 4 or nicotinic acid to the growth medium or by culture at lower temperatures (25°C), resulting in the Bvg Ϫ mode, a phenomenon known as modulation (26).…”

Section: Importancementioning

confidence: 99%

A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg ⁻ Mode Bordetella pertussis

et al. 2018

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In , two serologically distinct fimbriae, FIM2 and FIM3, undergo on/off phase variation independently of each other via variation in the lengths of C stretches in the promoters for their major subunit genes, and These two promoters are also part of the BvgAS virulence regulon and therefore, if in an on configuration, are activated by phosporylated BvgA (BvgA~P) under normal growth conditions (Bvg mode) but not in the Bvg mode, inducible by growth in medium containing MgSO or other compounds, termed modulators. In the Tohama I strain (FIM2 FIM3), the promoter is in the off state. However, a high level of transcription of the gene is observed in the Bvg mode. In this study, we provide an explanation for this anomalous behavior by defining a Bvg-repressed promoter (BRP), located approximately 400 bp upstream of the P transcriptional start. Although transcription of the gene in the Bvg mode resulted in Fim3 translation, as measured by LacZ translational fusions, no accumulation of Fim3 protein was detectable. We propose that Fim3 protein resulting from translation of mRNA driven by BRP in the Bvg mode is unstable due to a lack of the fimbrial assembly apparatus encoded by the genes, located within the operon, and therefore is not expressed in the Bvg mode. In , the promoter P-15C for the major fimbrial subunit gene is activated by the two-component system BvgAS in the Bvg mode but not in the Bvg mode. However, many transcriptional profiling studies have shown that is transcribed in the Bvg mode even when P is in a nonpermissive state (P-13C), suggesting the presence of a reciprocally regulated element upstream of P Here, we provide evidence that BRP is the cause of this anomalous behavior of Although BRP effects-like transcription of in the Bvg mode, it does not lead to stable production of FIM3 fimbriae, because expression of the chaperone and usher proteins FimB and FimC occurs only in the Bvg mode.

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Section: Importancementioning

confidence: 99%

A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg ⁻ Mode Bordetella pertussis

et al. 2018

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“…BvgS is in a kinase mode of activity in the basal state at 37°C. In the laboratory, the addition of modulators, such as MgSO 4 or nicotinate, or conditions of low temperature or nutrient restriction shift the bacteria to the Bvg − , avirulent phase ( 12 – 16 ). By using a Phos-Tag assay, we have shown that the dephosphorylation of BvgA is much faster after the addition of nicotinate to bacteria than when it occurs spontaneously, indicating that BvgS acts as a phosphatase in the Bvg − phase ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in Bordetella

Lesne

Krammer

Dupré

et al. 2016

mBio

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The two-component system BvgAS controls the expression of the virulence regulon of Bordetella pertussis. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that precede the dimerization-histidine-phosphotransfer domain of the kinase. BvgS homologs have a similar domain organization, or they harbor only a predicted coiled coil between the transmembrane and the dimerization-histidine-phosphotransfer domains. Here, we show that the 2-helix coiled coil of BvgS regulates the enzymatic activity in a mechanical manner. Its marginally stable hydrophobic interface enables a switch between a state of great rotational dynamics in the kinase mode and a more rigid conformation in the phosphatase mode in response to signal perception by the periplasmic domains. We further show that the activity of BvgS is controlled in the same manner if its PAS domain is replaced with the natural α-helical sequences of PAS-less homologs. Clamshell motions of the Venus flytrap domains trigger the shift of the coiled coil’s dynamics. Thus, we have uncovered a general mechanism of regulation for the BvgS family of Venus flytrap-containing two-component sensor kinases.

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“…The fact that BvgS contains three putative signal perception domains and therefore has the potential to integrate multiple distinct environmental signals has been known for 20 years (21, 37, 38). To date, however, roles only for the VFT domains have been identified (15)(16)(17). Studies investigating the purpose of the PAS domain have suggested a role only in transducing signals sensed by the VFTs to the cytoplasmic signaling domains (25,26).…”

Section: Discussionmentioning

confidence: 99%

“…Hence the "default" state for BvgS is one in which it is an active kinase. Binding of NA to VFT2 alters its conformation, and this change is apparently transduced across the membrane, which is proposed to cause reversal of the phosphorelay, resulting in the dephosphorylation of BvgA and a shift to the Bvgphase (17).…”

Section: Figmentioning

confidence: 99%

The BvgS PAS Domain, an Independent Sensory Perception Module in the Bordetella bronchiseptica BvgAS Phosphorelay

Sobran

Cotter

2019

J Bacteriol

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To detect and respond to the diverse environments they encounter, bacteria often use two-component regulatory systems (TCS) to coordinate essential cellular processes required for survival. In pathogenic Bordetella species, the BvgAS TCS regulates expression of hundreds of genes, including those encoding all known protein virulence factors, and its kinase activity is essential for respiratory infection. Maintenance of BvgS kinase activity in the lower respiratory tract (LRT) depends on the function of another TCS, PlrSR. While the periplasmic Venus flytrap domains of BvgS have been implicated in responding to so-called modulating signals in vitro (nicotinic acid and MgSO4), a role for the cytoplasmic Per-Arnt-Sim (PAS) domain in signal perception has not previously been demonstrated. By comparing B. bronchiseptica strains with mutations in the PAS domain-encoding region of bvgS with wild-type bacteria in vitro and in vivo, we found that although the PAS domain is not required to sense modulating signals in vitro, it is required for the inactivation of BvgS that occurs in the absence of PlrS in the LRTs of mice, suggesting that the BvgS PAS domain functions as an independent signal perception domain. Our data also indicate that the BvgS PAS domain is important for controlling absolute levels of BvgS kinase activity and the efficiency of the response to modulating signals in vitro. Our results provide evidence that BvgS integrates sensory inputs from both the periplasm and the cytoplasm to control precise gene expression patterns under diverse environmental conditions. IMPORTANCE Despite high rates of vaccination, pertussis, a severe, highly contagious respiratory disease caused by the bacterium Bordetella pertussis, has reemerged as a significant health threat. In Bordetella pertussis and the closely related species Bordetella bronchiseptica, activity of the BvgAS two-component regulatory system is critical for colonization of the mammalian respiratory tract. We show here that the cytoplasmic PAS domain of BvgS can function as an independent signal perception domain that influences BvgS activity in response to environmental conditions. Our work is significant because it reveals a critical, yet previously unrecognized, role for the PAS domain in the BvgAS phosphorelay and provides a greater understanding of virulence regulation in Bordetella.

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Signal Transduction by BvgS Sensor Kinase

Abstract: Background:The sensor kinase BvgS controls Bordetella virulence and is modulated by nicotinate.

Cited by 19 publications

References 48 publications

A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg ⁻ Mode Bordetella pertussis

A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg ⁻ Mode Bordetella pertussis

Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in Bordetella

The BvgS PAS Domain, an Independent Sensory Perception Module in the Bordetella bronchiseptica BvgAS Phosphorelay

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Signal Transduction by BvgS Sensor Kinase

Abstract: Background:The sensor kinase BvgS controls Bordetella virulence and is modulated by nicotinate.

Cited by 19 publications

References 48 publications

A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg − Mode Bordetella pertussis

A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg − Mode Bordetella pertussis

Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in Bordetella

The BvgS PAS Domain, an Independent Sensory Perception Module in the Bordetella bronchiseptica BvgAS Phosphorelay

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A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg ⁻ Mode Bordetella pertussis

A Novel Bvg-Repressed Promoter Causes vrg -Like Transcription of fim3 but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg ⁻ Mode Bordetella pertussis