Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract

M. Ashley Bone, Aaron J. Wilk, Andrew I. Perault, Sara A. Marlatt, Erich V. Scheller, Rebecca Anthouard, Qing Chen, Scott Stibitz, Peggy A. Cotter, Steven M. Julio

Research output: Contribution to journalArticle

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Abstract

Bacterial pathogens coordinate virulence using two-component regulatory systems (TCS). The Bordetella virulence gene (BvgAS) phosphorelay-type TCS controls expression of all known protein virulence factor-encoding genes and is considered the "master virulence regulator" in Bordetella pertussis, the causal agent of pertussis, and related organisms, including the broad host range pathogen Bordetella bronchiseptica. We recently discovered an additional sensor kinase, PlrS [for persistence in the lower respiratory tract (LRT) sensor], which is required for B. bronchiseptica persistence in the LRT. Here, we show that PlrS is required for BvgAS to become and remain fully active in mouse lungs but not the nasal cavity, demonstrating that PlrS coordinates virulence specifically in the LRT. PlrS is required for LRT persistence even when BvgAS is rendered constitutively active, suggesting the presence of BvgAS-independent, PlrS-dependent virulence factors that are critical for bacterial survival in the LRT. We show that PlrS is also required for persistence of the human pathogen B. pertussis in the murine LRT and we provide evidence that PlrS most likely functions via the putative cognate response regulator PlrR. These data support a model in which PlrS senses conditions present in the LRT and activates PlrR, which controls expression of genes required for the maintenance of BvgAS activity and for essential BvgAS-independent functions. In addition to providing a major advance in our understanding of virulence regulation in Bordetella, which has served as a paradigm for several decades, these results indicate the existence of previously unknown virulence factors that may serve as new vaccine components and therapeutic or diagnostic targets.

LanguageEnglish (US)
PagesE1519-E1527
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number8
DOIs
StatePublished - Feb 21 2017

Fingerprint

Bordetella
Respiratory System
Virulence
Virulence Factors
Bordetella bronchiseptica
Bordetella pertussis
Whooping Cough
Nasal Cavity
Host Specificity
Genes
Phosphotransferases
Vaccines
Maintenance
Gene Expression
Lung
Survival

Keywords

  • Bordetella
  • Gene regulation
  • Respiratory infection
  • Two-component system
  • Virulence

ASJC Scopus subject areas

  • General

Cite this

Bone, M. A., Wilk, A. J., Perault, A. I., Marlatt, S. A., Scheller, E. V., Anthouard, R., ... Julio, S. M. (2017). Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract. Proceedings of the National Academy of Sciences of the United States of America, 114(8), E1519-E1527. DOI: 10.1073/pnas.1609565114

Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract. / Bone, M. Ashley; Wilk, Aaron J.; Perault, Andrew I.; Marlatt, Sara A.; Scheller, Erich V.; Anthouard, Rebecca; Chen, Qing; Stibitz, Scott; Cotter, Peggy A.; Julio, Steven M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 8, 21.02.2017, p. E1519-E1527.

Research output: Contribution to journalArticle

Bone, MA, Wilk, AJ, Perault, AI, Marlatt, SA, Scheller, EV, Anthouard, R, Chen, Q, Stibitz, S, Cotter, PA & Julio, SM 2017, 'Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract' Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 8, pp. E1519-E1527. DOI: 10.1073/pnas.1609565114
Bone, M. Ashley ; Wilk, Aaron J. ; Perault, Andrew I. ; Marlatt, Sara A. ; Scheller, Erich V. ; Anthouard, Rebecca ; Chen, Qing ; Stibitz, Scott ; Cotter, Peggy A. ; Julio, Steven M./ Bordetella PlrSR regulatory system controls BvgAS activity and virulence in the lower respiratory tract. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 8. pp. E1519-E1527
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abstract = "Bacterial pathogens coordinate virulence using two-component regulatory systems (TCS). The Bordetella virulence gene (BvgAS) phosphorelay-type TCS controls expression of all known protein virulence factor-encoding genes and is considered the {"}master virulence regulator{"} in Bordetella pertussis, the causal agent of pertussis, and related organisms, including the broad host range pathogen Bordetella bronchiseptica. We recently discovered an additional sensor kinase, PlrS [for persistence in the lower respiratory tract (LRT) sensor], which is required for B. bronchiseptica persistence in the LRT. Here, we show that PlrS is required for BvgAS to become and remain fully active in mouse lungs but not the nasal cavity, demonstrating that PlrS coordinates virulence specifically in the LRT. PlrS is required for LRT persistence even when BvgAS is rendered constitutively active, suggesting the presence of BvgAS-independent, PlrS-dependent virulence factors that are critical for bacterial survival in the LRT. We show that PlrS is also required for persistence of the human pathogen B. pertussis in the murine LRT and we provide evidence that PlrS most likely functions via the putative cognate response regulator PlrR. These data support a model in which PlrS senses conditions present in the LRT and activates PlrR, which controls expression of genes required for the maintenance of BvgAS activity and for essential BvgAS-independent functions. In addition to providing a major advance in our understanding of virulence regulation in Bordetella, which has served as a paradigm for several decades, these results indicate the existence of previously unknown virulence factors that may serve as new vaccine components and therapeutic or diagnostic targets.",
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AU - Scheller,Erich V.

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