Central Role of the BvgS Receiver as a Phosphorylated Intermediate in a Complex Two-component Phosphorelay

Uhl, Michaël; Miller, Jeff F.

doi:10.1074/jbc.271.52.33176

Cited by 104 publications

(107 citation statements)

References 33 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…5A, Table 2). This is probably because of the phosphatase activity recently detected in the BvgS receiver domain (Uhl and Miller, 1996b), which is obviously absent from the EvgS receiver.…”

Section: Phosphorylation Of Isolated Signal Transduction Modulesmentioning

confidence: 99%

Specificity of the BvgAS and EvgAS phosphorelay is mediated by the C‐terminal HPt domains of the sensor proteins

Perraud

Kimmel

Weiss

et al. 1998

Molecular Microbiology

View full text Add to dashboard Cite

SummaryDespite the presence of highly conserved signalling modules, significant cross-communication between different two-component systems has only rarely been observed. Domain swapping and the characterization of liberated signalling modules enabled us to characterize in vitro the protein domains that mediate specificity and are responsible for the high fidelity in the phosphorelay of the unorthodox Bvg and Evg twocomponent systems. Under equimolar conditions, significant in vitro phosphorylation of purified BvgA and EvgA proteins was only obtained by their histidine kinases, BvgS and EvgS respectively. One hybrid histidine kinase consisting of the BvgS transmitter and HPt domains and of the EvgS receiver domain (BvgS-TO-EvgS-R) was able to phosphorylate BvgA but not EvgA. In contrast, the hybrid protein consisting of the BvgS transmitter and the EvgS receiver and HPt domains (BvgS-T-EvgS-RO) was unable to phosphorylate BvgA but efficiently phosphorylated EvgA. These results demonstrate that the C-terminal HPt domains of the sensor proteins endow the unorthodox twocomponent systems with a high specificity for the corresponding regulator protein. In the case of the response regulators, the receiver but not the output domains contribute to the specific interaction with the histidine kinases, because a hybrid protein consisting of the EvgA receiver and the BvgA output domain could only be phosphorylated by the EvgS protein.

show abstract

“…5A, Table 2). This is probably because of the phosphatase activity recently detected in the BvgS receiver domain (Uhl and Miller, 1996b), which is obviously absent from the EvgS receiver.…”

Section: Phosphorylation Of Isolated Signal Transduction Modulesmentioning

confidence: 99%

Specificity of the BvgAS and EvgAS phosphorelay is mediated by the C‐terminal HPt domains of the sensor proteins

Perraud

Kimmel

Weiss

et al. 1998

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…Upon phosphorylation, BvgA binds to the promoters of the virulence genes, inducing transcription of those genes (5-7, 9, 16, 29). Although the signals sensed by BvgS in vivo are unknown, it has been shown that when B. pertussis is grown at low temperatures, or in the presence of MgSO 4 or nicotinic acid, the BvgS-mediated phospho-transfer reactions are inhibited, and the expression of the bvg-activated genes is down regulated (a condition referred to as modulation) (36,38,39).…”

mentioning

confidence: 99%

“…BvgS is a membrane-spanning protein that presumably acts as a sensor of the external environment, and BvgA is a soluble transcriptional activator. When B. pertussis is grown under normal laboratory conditions in rich media at 37°C, the BvgS protein is autophosphorylated and mediates the phosphorylation of BvgA through a series of phospho-transfer reactions (36,38,39). Upon phosphorylation, BvgA binds to the promoters of the virulence genes, inducing transcription of those genes (5-7, 9, 16, 29).…”

mentioning

confidence: 99%

Activation of the vrg6 Promoter of Bordetella pertussis by RisA

2005

View full text Add to dashboard Cite

“…Under these conditions, the kinase and phosphotransfer activities of BvgS are high. Therefore, this is considered a default "on-state" since BvgA is phosphorylated without any known chemical stimuli (19). Phosphorylation of BvgA, which is absolutely required for adaptation and colonization in respiratory tracts of experimental animals, results in BvgA~P dimerization and transcriptional activation of key vag promoters (20,21).…”

mentioning

confidence: 99%

The BvgAS Regulon of Bordetella pertussis

Moon

Bonocora

Kim

et al. 2017

mBio

120

View full text Add to dashboard Cite

Nearly all virulence factors in Bordetella pertussis are activated by a master two-component system, BvgAS, composed of the sensor kinase BvgS and the response regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P), and virulence-activated genes (vags) are expressed [Bvg(ϩ) mode]. When BvgS is inactive and BvgA is not phosphorylated, virulence-repressed genes (vrgs) are induced [Bvg(Ϫ) mode]. Here, we have used transcriptome sequencing (RNA-seq) and reverse transcription-quantitative PCR (RT-qPCR) to define the BvgAS-dependent regulon of B. pertussis Tohama I. Our analyses reveal more than 550 BvgA-regulated genes, of which 353 are newly identified. BvgA-activated genes include those encoding two-component systems (such as kdpED), multiple other transcriptional regulators, and the extracytoplasmic function (ECF) sigma factor brpL, which is needed for type 3 secretion system (T3SS) expression, further establishing the importance of BvgA~P as an apex regulator of transcriptional networks promoting virulence. Using in vitro transcription, we demonstrate that the promoter for brpL is directly activated by BvgA~P. BvgA-FeBABE cleavage reactions identify BvgA~P binding sites centered at positions Ϫ41.5 and Ϫ63.5 in bprL. Most importantly, we show for the first time that genes for multiple and varied metabolic pathways are significantly upregulated in the B. pertussis Bvg(Ϫ) mode. These include genes for fatty acid and lipid metabolism, sugar and amino acid transporters, pyruvate dehydrogenase, phenylacetic acid degradation, and the glycolate/glyoxylate utilization pathway. Our results suggest that metabolic changes in the Bvg(Ϫ) mode may be participating in bacterial survival, transmission, and/or persistence and identify over 200 new vrgs that can be tested for function.IMPORTANCE Within the past 20 years, outbreaks of whooping cough, caused by Bordetella pertussis, have led to respiratory disease and infant mortalities, despite good vaccination coverage. This is due, at least in part, to the introduction of a less effective acellular vaccine in the 1990s. It is crucial, then, to understand the molecular basis of B. pertussis growth and infection. The two-component system BvgA (response regulator)/BvgS (histidine kinase) is the master regulator of B. pertussis virulence genes. We report here the first RNA-seq analysis of the BvgAS regulon in B. pertussis, revealing that more than 550 genes are regulated by BvgAS. We show that genes for multiple and varied metabolic pathways are highly regulated in the Bvg(Ϫ) mode (absence of BvgA phosphorylation). Our results suggest that metabolic changes in the Bvg(Ϫ) mode may be participating in bacterial survival, transmission, and/or persistence.

show abstract

Central Role of the BvgS Receiver as a Phosphorylated Intermediate in a Complex Two-component Phosphorelay

Cited by 104 publications

References 33 publications

Specificity of the BvgAS and EvgAS phosphorelay is mediated by the C‐terminal HPt domains of the sensor proteins

Specificity of the BvgAS and EvgAS phosphorelay is mediated by the C‐terminal HPt domains of the sensor proteins

Activation of the vrg6 Promoter of Bordetella pertussis by RisA

The BvgAS Regulon of Bordetella pertussis

Contact Info

Product

Resources

About