<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
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
Affiliations
Shihono Teruya
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Yukihiro Hiramatsu
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Keiji Nakamura
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Aya Fukui-Miyazaki
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Kentaro Tsukamoto
Department of Microbiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
Noriko Shinoda
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Daisuke Motooka
Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Shota Nakamura
Department of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Keisuke Ishigaki
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Naoaki Shinzawa
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Takashi Nishida
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Fuminori Sugihara
Central Instrumentation Laboratory, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Yusuke Maeda
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
Yasuhiko Horiguchi
Department of Molecular Bacteriology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
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.
