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ニシダ タカシ
NISHIDA Takashi
西田 隆司 所属 医学部 医学科 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Bordetella Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses CaV3.1 as the Cell Surface Receptor. |
| 掲載誌名 | 正式名：mBio 略 称：mBio ISSNコード：21507511 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 11(2),pp.e03146 |
| 著者・共著者 | 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 |
| 発行年月 | 2020/03 |
| 概要 | 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.IMPORTANCEBordetella 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. |
| DOI | 10.1128/mBio.03146-19 |
| PMID | 32209694 |