Characterization of Serotype CD Mosaic Botulinum Neurotoxin in Comparison with Serotype C and A.

Autor: Miyashita SI; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Karatsu S; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Fujiishi M; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Huang IH; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Nagashima Y; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Morobishi T; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Hosoya K; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Hata T; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan., Dong M; Department of Urology, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA., Sagane Y; Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan.
Jazyk: angličtina
Zdroj: Toxins [Toxins (Basel)] 2023 Feb 03; Vol. 15 (2). Date of Electronic Publication: 2023 Feb 03.
DOI: 10.3390/toxins15020123
Abstrakt: Botulinum neurotoxin (BoNT), produced by Clostridium botulinum , cleaves proteins involved in neurotransmitter release, thereby triggering flaccid paralyses, which are responsible for botulism. BoNT is classified into seven serotypes (BoNT/A-G); BoNT/A and BoNT/B are used as medical therapeutics and anti-wrinkle reagents. In this study, we investigated the efficacy of BoNT/CD, a mosaic toxin of BoNT/C and BoNT/D, to assess its potential as a therapeutic alternative for BoNT/A. In a cultured neuron assay, BoNT/CD cleaved syntaxin and SNAP-25 with higher efficacy than BoNT/C and BoNT/A. Intramuscularly administrated BoNT/CD induced dose-dependent muscle paralysis, and the paralysis lasted ~21 days in a mouse digit abduction score assay (BoNT/A-induced paralysis lasted ~30 days). BoNT/C failed to induce local paralysis without systemic toxicity. Multiple alignment analyses of the amino acid sequences of the receptor binding domain (H C ) of eight BoNT/CDs and two BoNT/Ds showed sequence clustering in five groups. Comparing BoNT/CD strain 003-9 (BoNT/CD 003-9 ) and strain 6813 (BoNT/CD 6813 ) showed that both BoNT/CDs displayed similar efficacies in cultured neurons, but BoNT/CD 003-9 displayed higher efficacy in a mouse model than BoNT/CD 6813 . These findings suggest that BoNT/CD may be a potential alternative for patients who do not respond to existing BoNT-based therapeutics.
Databáze: MEDLINE
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