Characterization of Serotype CD Mosaic Botulinum Neurotoxin in Comparison with Serotype C and A.
Characterization of Serotype CD Mosaic Botulinum Neurotoxin in Comparison with Serotype C and A.
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DOI：
10.3390/toxins15020123
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发表时间：
2023-02-03
期刊：
影响因子：
4.2
通讯作者：
Sagane Y
中科院分区：
文献类型：
--
作者：
Miyashita SI;Karatsu S;Fujiishi M;Huang IH;Nagashima Y;Morobishi T;Hosoya K;Hata T;Dong M;Sagane Y
肉毒杆菌神经毒素（BoNT）由肉毒梭菌产生，切割参与神经递质释放的蛋白质，从而引发弛缓性麻痹，这是肉毒中毒的原因。BoNT分为七种血清型（BoNT/A-G）; BoNT/A和BoNT/B用作医疗和抗皱试剂。在这项研究中，我们研究了BoNT/CD（BoNT/C和BoNT/D的嵌合毒素）的疗效，以评估其作为BoNT/A治疗替代品的潜力。在培养的神经元测定中，BoNT/CD以比BoNT/C和BoNT/A更高的功效切割突触融合蛋白和SNAP-25。肌肉内施用BoNT/CD诱导剂量依赖性肌肉麻痹，并且在小鼠手指外展评分测定中麻痹持续约21天（BoNT/A诱导的麻痹持续约30天）。BoNT/C未能诱导局部麻痹而无全身毒性。8个BoNT/CD和2个BoNT/Ds的受体结合域（HC）的氨基酸序列的多重比对分析显示在5组中的序列聚类。比较BoNT/CD菌株003-9（BoNT/CD 003 -9）和菌株6813（BoNT/CD 6813）显示，两种BoNT/CD在培养的神经元中显示出相似的功效，但BoNT/CD 003 -9在小鼠模型中显示出比BoNT/CD 6813更高的功效。这些研究结果表明，BoNT/CD可能是对现有BoNT疗法无反应的患者的潜在替代方案。
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 (HC) of eight BoNT/CDs and two BoNT/Ds showed sequence clustering in five groups. Comparing BoNT/CD strain 003-9 (BoNT/CD003-9) and strain 6813 (BoNT/CD6813) showed that both BoNT/CDs displayed similar efficacies in cultured neurons, but BoNT/CD003-9 displayed higher efficacy in a mouse model than BoNT/CD6813. These findings suggest that BoNT/CD may be a potential alternative for patients who do not respond to existing BoNT-based therapeutics.
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影响因子：
4.8
作者：
Hasegawa, Kimiko;Watanabe, Toshihiro;Ohyama, Tohru
通讯作者：
Ohyama, Tohru
影响因子：
56.9
作者：
Dong, M;Yeh, F;Chapman, ER
通讯作者：
Chapman, ER
影响因子：
4.2
作者：
Fonfria E;Maignel J;Lezmi S;Martin V;Splevins A;Shubber S;Kalinichev M;Foster K;Picaut P;Krupp J
通讯作者：
Krupp J
影响因子：
2.8
作者：
Aoki, KR
通讯作者：
Aoki, KR
影响因子：
8.6
作者：
Eleopra, R;Tugnoli, V;Montecucco, C
通讯作者：
Montecucco, C