掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Clostridium argentinense produces botulinum neurotoxin type G (BoNT/G). We sequenced and analyzed the plasmid harboring the bont/G gene, designated pCAG, in C. argentinense strain 2740. The pCAG consisted of 140,070 bp containing the bont/G gene cluster. Although this gene cluster showed high similarities in its DNA sequence and ORF arrangement to those of other bont gene clusters, the other regions of the plasmid did not. A phylogenetic study suggested that pCAG had a unique evolutionary history compared with other clostridial bont-harboring plasmids. This suggests that pCAG is possibly a novel type of plasmid expressing the bont/G gene in C. argentinense.

DOI： 10.1016/j.anaerobe.2020.102281

PubMed

神経細胞へのボツリヌス神経毒素(BoNT)侵入と関連のあるN末端(HN)領域について調べるため、BoNT血清型A(BoNT/A1)とBoNT/A2のHNをBoNT/A2とBoNT/A1のHNに置換したキメラBoNP/A121とBoNT/A212を作成した。野生型とキメラのBoNT/Aの毒性は類似していた。しかし、神経細胞のSNAP-25開裂活性は異なっていた。BoNP/A121とBoNT/A2は同じような高いSNAP-25開裂活性を示した。以上より、BoNT/A1よりもBoNT/A2の活性が高いのは、BoNT/A2HNによると考えられた。

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Botulinum neurotoxin (BoNT) is the most potent natural toxin known. Of the seven BoNT serotypes (A to G), types A, B, E, and F cause human botulism. Treatment of human botulism requires the development of effective toxin-neutralizing antibodies without side effects such as serum sickness and anaphylaxis. In this study, we generated fully human monoclonal antibodies (HuMAbs) against serotype B BoNT (BoNT/B1) using a murine-human chimera fusion partner cell line named SPYMEG. Of these HuMAbs, M2, which specifically binds to the light chain of BoNT/B1, showed neutralization activity in a mouse bioassay (approximately 10 i.p. LD50/100 µg of antibody), and M4, which binds to the C-terminal of heavy chain, showed partial protection. The combination of two HuMAbs, M2 (1.25 µg) and M4 (1.25 µg), was able to completely neutralize BoNT/B1 (80 i.p. LD50) with a potency greater than 80 i.p. LD50/2.5 µg of antibodies, and was effective both prophylactically and therapeutically in the mouse model of botulism. Moreover, this combination showed broad neutralization activity against three type B subtypes, namely BoNT/B1, BoNT/B2, and BoNT/B6. These data demonstrate that the combination of M2 and M4 is promising in terms of a foundation for new human therapeutics for BoNT/B intoxication.

DOI： 10.3390/toxins12050302

PubMed

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共著区分：共著  

共著区分：共著