The BvgAS Regulon of
            <i>Bordetella pertussis</i>

Moon, Kyung Ho; Bonocora, Richard P.; Kim, David D.; Chen, Qing; Wade, Joseph T.; Stibitz, Scott; Hinton, Deborah M.

doi:10.1128/mbio.01526-17

Cited by 58 publications

(133 citation statements)

References 67 publications

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“…Transcriptomics is very routinely employed to elucidate the regulons and functions of TCSs. Typically, gene expression in a deletion or knock‐out mutant in either the RR gene (Liu et al ., ; Low et al ., ; Antoraz et al ., ) or both HK–RR genes (Richmond et al ., ; Chen et al ., ; Moon et al ., ) is compared with that of the wild‐type (WT) strain (Fig. ).…”

Section: Expression Profiling Methodsmentioning

confidence: 99%

Tools to map target genes of bacterial two‐component system response regulators

Rajeev

Garber

Mukhopadhyay

2020

Environ Microbiol Rep

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Studies on bacterial physiology are incomplete without knowledge of the signalling and regulatory systems that a bacterium uses to sense and respond to its environment. Two-component systems (TCSs) are among the most prevalent bacterial signalling systems, and they control essential and secondary physiological processes; however, even in model organisms, we lack a complete understanding of the signals sensed, the phosphotransfer partners and the functions regulated by these systems. In this review, we discuss several tools to map the genes targeted by transcriptionally acting TCSs. Many of these tools have been used for studying individual TCSs across diverse species, but systematic approaches to delineate entire signalling networks have been very few. Since genome sequences and high-throughput technologies are now readily available, the methods presented here can be applied to characterize the entire DNA-binding TCS signalling network in any bacterial species and are especially useful for non-model environmental bacteria.

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Section: Expression Profiling Methodsmentioning

confidence: 99%

Tools to map target genes of bacterial two‐component system response regulators

Rajeev

Garber

Mukhopadhyay

2020

Environ Microbiol Rep

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“…phorylated (11), presumably due to the reversal of the BvgAS phosphorelay, resulting in the Bvgphase. The Bvgphase is characterized by the expression of genes that are repressed by BvgAϳP (termed vir-repressed genes [vrgs]) and lack of expression of vags (10). In B. bronchiseptica, flagellar regulon genes, including the flagellin-encoding gene flaA, are vrgs (12).…”

Section: Figmentioning

confidence: 99%

“…BvgAϳP forms homodimers capable of binding DNA and activating or repressing gene transcription (9). Under these conditions, BvgAϳP levels are high, and the bacteria express the Bvg ϩ phase, which is characterized by transcription of all known vir-activated genes (vags), including those encoding critical virulence factors (10). When Bordetella is grown at 25°C or at 37°C in the presence of millimolar concentrations of nicotinic acid (NA) or magnesium sulfate (MgSO 4 ), BvgA is unphos-…”

mentioning

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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“…BvgA~P forms homodimers capable of binding DNA and activating or repressing gene transcription (10). Under these conditions, BvgA~P levels are high and the bacteria express the Bvg + phase, which is characterized by transcription of all known virulence-activated genes ( vag s), including those encoding critical virulence factors (11). When Bordetella are grown at 25°C or at 37°C in the presence of millimolar concentrations of nicotinic acid (NA) or magnesium sulfate (MgSO 4 ), the BvgS phosphorelay is reversed and BvgS dephosphorylates BvgA, resulting in the Bvg − phase.…”

Section: Introductionmentioning

confidence: 99%

“…When Bordetella are grown at 25°C or at 37°C in the presence of millimolar concentrations of nicotinic acid (NA) or magnesium sulfate (MgSO 4 ), the BvgS phosphorelay is reversed and BvgS dephosphorylates BvgA, resulting in the Bvg − phase. The Bvg − phase is characterized by the expression of genes that are repressed by BvgA~P (termed virulence-repressed genes ( vrg s)) and lack of expression of vag s (11). In B. bronchiseptica , flagellar regulon genes, including the flagellin-encoding gene flaA , are vrgs (12).…”

Section: Introductionmentioning

confidence: 99%

The BvgS PAS domain: an independent sensory perception module in theBordetellaBvgAS phosphorelay

Sobran

Cotter

2019

Preprint

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24 25 To detect and respond to the diverse environments they encounter, bacteria often use two-26 component regulatory systems (TCSs) to coordinate essential cellular processes required for 27 survival. In pathogenic Bordetella species, the BvgAS TCS regulates expression of hundreds of 28 genes, including those encoding all known protein virulence factors, and its kinase activity is 29 essential for respiratory infection. Maintenance of BvgS kinase activity in the lower respiratory 30 tract (LRT) depends on the function of another TCS, PlrSR. While the periplasmic venus fly-trap 31 domains of BvgS have been implicated in responding to so-called modulating signals in vitro 32 (nicotinic acid and MgSO 4 ), a role for the cytoplasmic Per-Arnt-Sim (PAS) domain in signal 33 perception has not previously been demonstrated. By comparing B. bronchiseptica strains with 34 mutations in the PAS domain-encoding region of bvgS with wild-type bacteria in vitro and in 35vivo, we found that although the PAS domain is not required to sense modulating signals in 36 vitro, it is required for the inactivation of BvgS that occurs in the absence of PlrS in the LRT of 37 mice, suggesting that the BvgS PAS domain functions as an independent signal perception 38 domain. Our data also indicate that the BvgS PAS domain is important for controlling absolute 39 levels of BvgS kinase activity and the efficiency of the response to modulating signals in vitro. 40Our results indicate that BvgS is capable of integrating sensory inputs from both the periplasm 41 and the cytoplasm to control precise gene expression patterns in diverse environmental 42 conditions. 43 44 Importance 45 46 Despite high rates of vaccination, Pertussis, a severe, highly contagious respiratory disease, 47 caused by the bacterium Bordetella pertussis, has reemerged as a significant health threat. In 48Bordetella pertussis and the closely related species, Bordetella bronchiseptica, activity of the 49 BvgAS two-component regulatory system is critical for colonization of the human respiratory 50 tract and other mammalian hosts, respectively. Here we show that the cytoplasmic PAS domain 51 of BvgS can function as an independent signal perception domain that is capable of integrating 52 environmental signals that influence overall BvgS activity. Our work is significant as it reveals a 53critical, yet previously unrecognized role, for the PAS domain in the BvgAS phosphorelay and 54 provides a greater understanding of virulence regulation in Bordetella. 55 56 Introduction 57

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The BvgAS Regulon of Bordetella pertussis

Cited by 58 publications

References 67 publications

Tools to map target genes of bacterial two‐component system response regulators

Tools to map target genes of bacterial two‐component system response regulators

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

The BvgS PAS domain: an independent sensory perception module in theBordetellaBvgAS phosphorelay

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