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.