BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats

ABSTRACT Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Keiji Nakamura, Noriko Shinoda, Yukihiro Hiramatsu, Shinya Ohnishi, Shigeki Kamitani, Yoshitoshi Ogura, Tetsuya Hayashi, Yasuhiko Horiguchi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Bordetella BspR/BtrA cough Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4859917f5bfa4da89f817ab28213c364
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4859917f5bfa4da89f817ab28213c364
record_format	dspace
spelling	oai:doaj.org-article:4859917f5bfa4da89f817ab28213c3642021-11-15T15:22:22ZBspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats10.1128/mSphere.00093-192379-5042https://doaj.org/article/4859917f5bfa4da89f817ab28213c3642019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00093-19https://doaj.org/toc/2379-5042ABSTRACT Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals that replicate coughing after Bordetella infection. Here, we present a coughing model of rats infected with B. bronchiseptica. Rats, which are one of natural hosts of B. bronchiseptica, were readily infected with the organisms and showed frequent coughing. B. pertussis also caused coughing in rats, which is consistent with previous reports, but the cough response was less apparent than the B. bronchiseptica-induced cough. By using the rat model, we demonstrated that adenylate cyclase toxin, dermonecrotic toxin, and the type III secretion system are not involved in cough production, but BspR/BtrA (different names for the same protein), an anti-σ factor, regulates the production of unknown factor(s) to cause coughing. Rat coughing was observed by inoculation of not only the living bacteria but also the bacterial lysates. Infection with bspR (btrA)-deficient strains caused significantly less frequent coughing than the wild type; however, intranasal inoculation of the lysates from a bspR (btrA)-deficient strain caused coughing similarly to the wild type, suggesting that BspR/BtrA regulates the production of the cough factor(s) only when the bacteria colonize host bodies. Moreover, the cough factor(s) was found to be heat labile and produced by B. bronchiseptica in the Bvg+ phase. We consider that our rat model provides insight into the pathogenesis of cough induced by the Bordetella infection. IMPORTANCE Whooping cough is a contagious respiratory disease caused by Bordetella pertussis. This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzing Bordetella-induced coughing is the lack of conventional animal models that replicate coughing. As Bordetella pertussis is highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected with B. bronchiseptica, which shares many virulence factors with B. pertussis. Using this rat model, we demonstrated that some of the major virulence factors of Bordetella are not involved in cough production, but an anti-σ factor, BspR/BtrA, of B. bronchiseptica regulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by which Bordetella induces cough.Keiji NakamuraNoriko ShinodaYukihiro HiramatsuShinya OhnishiShigeki KamitaniYoshitoshi OguraTetsuya HayashiYasuhiko HoriguchiAmerican Society for MicrobiologyarticleBordetellaBspR/BtrAcoughMicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bordetella BspR/BtrA cough Microbiology QR1-502
spellingShingle	Bordetella BspR/BtrA cough Microbiology QR1-502 Keiji Nakamura Noriko Shinoda Yukihiro Hiramatsu Shinya Ohnishi Shigeki Kamitani Yoshitoshi Ogura Tetsuya Hayashi Yasuhiko Horiguchi BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats
description	ABSTRACT Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals that replicate coughing after Bordetella infection. Here, we present a coughing model of rats infected with B. bronchiseptica. Rats, which are one of natural hosts of B. bronchiseptica, were readily infected with the organisms and showed frequent coughing. B. pertussis also caused coughing in rats, which is consistent with previous reports, but the cough response was less apparent than the B. bronchiseptica-induced cough. By using the rat model, we demonstrated that adenylate cyclase toxin, dermonecrotic toxin, and the type III secretion system are not involved in cough production, but BspR/BtrA (different names for the same protein), an anti-σ factor, regulates the production of unknown factor(s) to cause coughing. Rat coughing was observed by inoculation of not only the living bacteria but also the bacterial lysates. Infection with bspR (btrA)-deficient strains caused significantly less frequent coughing than the wild type; however, intranasal inoculation of the lysates from a bspR (btrA)-deficient strain caused coughing similarly to the wild type, suggesting that BspR/BtrA regulates the production of the cough factor(s) only when the bacteria colonize host bodies. Moreover, the cough factor(s) was found to be heat labile and produced by B. bronchiseptica in the Bvg+ phase. We consider that our rat model provides insight into the pathogenesis of cough induced by the Bordetella infection. IMPORTANCE Whooping cough is a contagious respiratory disease caused by Bordetella pertussis. This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzing Bordetella-induced coughing is the lack of conventional animal models that replicate coughing. As Bordetella pertussis is highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected with B. bronchiseptica, which shares many virulence factors with B. pertussis. Using this rat model, we demonstrated that some of the major virulence factors of Bordetella are not involved in cough production, but an anti-σ factor, BspR/BtrA, of B. bronchiseptica regulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by which Bordetella induces cough.
format	article
author	Keiji Nakamura Noriko Shinoda Yukihiro Hiramatsu Shinya Ohnishi Shigeki Kamitani Yoshitoshi Ogura Tetsuya Hayashi Yasuhiko Horiguchi
author_facet	Keiji Nakamura Noriko Shinoda Yukihiro Hiramatsu Shinya Ohnishi Shigeki Kamitani Yoshitoshi Ogura Tetsuya Hayashi Yasuhiko Horiguchi
author_sort	Keiji Nakamura
title	BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats
title_short	BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats
title_full	BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats
title_fullStr	BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats
title_full_unstemmed	BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats
title_sort	bspr/btra, an anti-σ factor, regulates the ability of <italic toggle="yes">bordetella bronchiseptica</italic> to cause cough in rats
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/4859917f5bfa4da89f817ab28213c364
work_keys_str_mv	AT keijinakamura bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats AT norikoshinoda bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats AT yukihirohiramatsu bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats AT shinyaohnishi bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats AT shigekikamitani bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats AT yoshitoshiogura bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats AT tetsuyahayashi bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats AT yasuhikohoriguchi bsprbtraanantisfactorregulatestheabilityofitalictoggleyesbordetellabronchisepticaitalictocausecoughinrats
_version_	1718428005679759360

BspR/BtrA, an Anti-σ Factor, Regulates the Ability of <italic toggle="yes">Bordetella bronchiseptica</italic> To Cause Cough in Rats

Ejemplares similares