<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor

ABSTRACT Dermonecrotic toxin (DNT) is one of the representative toxins produced by Bordetella pertussis, but its role in pertussis, B. pertussis infection, remains unknown. In this study, we identified the T-type voltage-gated Ca2+ channel CaV3.1 as the DNT receptor by CRISPR-Cas9-based genome-wide...

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Autores principales:	Shihono Teruya, Yukihiro Hiramatsu, Keiji Nakamura, Aya Fukui-Miyazaki, Kentaro Tsukamoto, Noriko Shinoda, Daisuke Motooka, Shota Nakamura, Keisuke Ishigaki, Naoaki Shinzawa, Takashi Nishida, Fuminori Sugihara, Yusuke Maeda, Yasuhiko Horiguchi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	pertussis dermonecrotic toxin receptor encephalopathy Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9697f89d3b9948dc8e71e8e9ee0e55ae
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spelling	oai:doaj.org-article:9697f89d3b9948dc8e71e8e9ee0e55ae2021-11-15T15:57:01Z<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor10.1128/mBio.03146-192150-7511https://doaj.org/article/9697f89d3b9948dc8e71e8e9ee0e55ae2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03146-19https://doaj.org/toc/2150-7511ABSTRACT Dermonecrotic toxin (DNT) is one of the representative toxins produced by Bordetella pertussis, but its role in pertussis, B. pertussis infection, remains unknown. In this study, we identified the T-type voltage-gated Ca2+ channel CaV3.1 as the DNT receptor by CRISPR-Cas9-based genome-wide screening. As CaV3.1 is highly expressed in the nervous system, the neurotoxicity of DNT was examined. DNT affected cultured neural cells and caused flaccid paralysis in mice after intracerebral injection. No neurological symptoms were observed by intracerebral injection with the other major virulence factors of the organisms, pertussis toxin and adenylate cyclase toxin. These results indicate that DNT has aspects of the neurotropic virulence factor of B. pertussis. The possibility of the involvement of DNT in encephalopathy, which is a complication of pertussis, is also discussed. IMPORTANCE Bordetella pertussis, which causes pertussis, a contagious respiratory disease, produces three major protein toxins, pertussis toxin, adenylate cyclase toxin, and dermonecrotic toxin (DNT), for which molecular actions have been elucidated. The former two toxins are known to be involved in the emergence of some clinical symptoms and/or contribute to the establishment of bacterial infection. In contrast, the role of DNT in pertussis remains unclear. Our study shows that DNT affects neural cells through specific binding to the T-type voltage-gated Ca2+ channel that is highly expressed in the central nervous system and leads to neurological disorders in mice after intracerebral injection. These data raise the possibility of DNT as an etiological agent for pertussis encephalopathy, a severe complication of B. pertussis infection.Shihono TeruyaYukihiro HiramatsuKeiji NakamuraAya Fukui-MiyazakiKentaro TsukamotoNoriko ShinodaDaisuke MotookaShota NakamuraKeisuke IshigakiNaoaki ShinzawaTakashi NishidaFuminori SugiharaYusuke MaedaYasuhiko HoriguchiAmerican Society for Microbiologyarticlepertussisdermonecrotic toxinreceptorencephalopathyMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	pertussis dermonecrotic toxin receptor encephalopathy Microbiology QR1-502
spellingShingle	pertussis dermonecrotic toxin receptor encephalopathy Microbiology QR1-502 Shihono Teruya Yukihiro Hiramatsu Keiji Nakamura Aya Fukui-Miyazaki Kentaro Tsukamoto Noriko Shinoda Daisuke Motooka Shota Nakamura Keisuke Ishigaki Naoaki Shinzawa Takashi Nishida Fuminori Sugihara Yusuke Maeda Yasuhiko Horiguchi <italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor
description	ABSTRACT Dermonecrotic toxin (DNT) is one of the representative toxins produced by Bordetella pertussis, but its role in pertussis, B. pertussis infection, remains unknown. In this study, we identified the T-type voltage-gated Ca2+ channel CaV3.1 as the DNT receptor by CRISPR-Cas9-based genome-wide screening. As CaV3.1 is highly expressed in the nervous system, the neurotoxicity of DNT was examined. DNT affected cultured neural cells and caused flaccid paralysis in mice after intracerebral injection. No neurological symptoms were observed by intracerebral injection with the other major virulence factors of the organisms, pertussis toxin and adenylate cyclase toxin. These results indicate that DNT has aspects of the neurotropic virulence factor of B. pertussis. The possibility of the involvement of DNT in encephalopathy, which is a complication of pertussis, is also discussed. IMPORTANCE Bordetella pertussis, which causes pertussis, a contagious respiratory disease, produces three major protein toxins, pertussis toxin, adenylate cyclase toxin, and dermonecrotic toxin (DNT), for which molecular actions have been elucidated. The former two toxins are known to be involved in the emergence of some clinical symptoms and/or contribute to the establishment of bacterial infection. In contrast, the role of DNT in pertussis remains unclear. Our study shows that DNT affects neural cells through specific binding to the T-type voltage-gated Ca2+ channel that is highly expressed in the central nervous system and leads to neurological disorders in mice after intracerebral injection. These data raise the possibility of DNT as an etiological agent for pertussis encephalopathy, a severe complication of B. pertussis infection.
format	article
author	Shihono Teruya Yukihiro Hiramatsu Keiji Nakamura Aya Fukui-Miyazaki Kentaro Tsukamoto Noriko Shinoda Daisuke Motooka Shota Nakamura Keisuke Ishigaki Naoaki Shinzawa Takashi Nishida Fuminori Sugihara Yusuke Maeda Yasuhiko Horiguchi
author_facet	Shihono Teruya Yukihiro Hiramatsu Keiji Nakamura Aya Fukui-Miyazaki Kentaro Tsukamoto Noriko Shinoda Daisuke Motooka Shota Nakamura Keisuke Ishigaki Naoaki Shinzawa Takashi Nishida Fuminori Sugihara Yusuke Maeda Yasuhiko Horiguchi
author_sort	Shihono Teruya
title	<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor
title_short	<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor
title_full	<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor
title_fullStr	<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor
title_full_unstemmed	<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor
title_sort	<italic toggle="yes">bordetella</italic> dermonecrotic toxin is a neurotropic virulence factor that uses ca<sub>v</sub>3.1 as the cell surface receptor
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9697f89d3b9948dc8e71e8e9ee0e55ae
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<italic toggle="yes">Bordetella</italic> Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses Ca<sub>V</sub>3.1 as the Cell Surface Receptor

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