权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of absorption of Clostridium botulinum toxins from the small infestine

小infestine对肉毒杆菌毒素的吸收分析

基本信息

批准号：
12670255
负责人：
OGUMA Keiji
金额：
$ 2.56万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670255/
关键词：
Clostridium botulinum Botulinum toxin Haemagglutinin Receptor Salic acid Sialy lactose Ga1β1-4 G1cNac Monoclonal antibody ムチン蛋白質

项目摘要

Clostridium botulinum strains produce seven immunologically distinct neurotoxins, from types A to G. The molecular mass (Mr) of all types of neurotoxins is approximately 150 kDa. The neurotoxins are associated with non-toxic component in cultures or in foods, and become large complexes designated progenitor toxins. Type, B, C, and D strains produce two forms of progenitor toxin, M (300 kDa, 12S toxin) and L (500 kDa, 16S toxin), and type A produces M, L, and LL toxins. The M toxin consists of a neurotoxin and a non-toxic component showing no haemagglutinin (HA) activity, which is described as non-toxic non-HA. The L toxin is formed by conjugation of M toxin with HA. The LL toxin is a dimer of L toxin. Recently we found that HA consists of four subcomponents designated HA1 (~33 kDa), HA2 (~17 kDa), HA3a (~23 kDa), and HA3b (~53 kDa), and that type C-L toxin is effectively absorbed from the small intestine than M toxin and neurotoxin. This time, binding of A-L and -LL toxins (designated HA^+-PT) and recombinant four HA subcomponents to erythrocytes or the epithelial cells of guinea pig-small intestine were analyzed. It became clear that HA^+-PTX bound epithelial cells and erythrocytes mainly via HA1, and its receptor was Galβ-1-4GlcNac. In case of type C, it seemed that L toxin bound to the cells via both HA1 and HA3b, and the receptor of HA1 and HA3b was sialyl lactose and sialic acid, respectively.The importance of C-HA1 for the binding of L toxin to the cells was further confirmed by analysing two mutant L toxins with low HA activity and by preparing monoclonal antibodies against HA1.

肉毒杆菌菌株产生7种免疫上不同的神经毒素，从A型到g型，所有类型的神经毒素的分子量（Mr）约为150 kDa。神经毒素与培养物或食物中的无毒成分相关联，并形成称为祖毒素的大型复合物。B型、C型和D型菌株产生两种形式的祖毒素，M （300 kDa， 12S毒素）和L （500 kDa， 16S毒素），A型产生M、L和LL毒素。M毒素由一种神经毒素和一种没有血凝素（HA）活性的无毒成分组成，被称为无毒非血凝素。L毒素是由M毒素与HA结合形成的。LL毒素是L毒素的二聚体。最近我们发现HA由HA1 （~33 kDa）、HA2 （~17 kDa）、HA3a （~23 kDa）和HA3b （~53 kDa）四个亚组分组成，并且C-L型毒素比M型毒素和神经毒素更容易被小肠吸收。这一次，我们分析了A-L和-LL毒素（指定HA^+-PT）和重组四种HA亚组分与豚鼠小肠红细胞或上皮细胞的结合。结果表明，HA^+-PTX主要通过HA1结合上皮细胞和红细胞，其受体为Galβ-1-4GlcNac。在C型中，L毒素似乎同时通过HA1和HA3b与细胞结合，HA1和HA3b的受体分别是唾液乳糖和唾液酸。通过分析两种低HA活性突变的L毒素，并制备抗HA1的单克隆抗体，进一步证实了C-HA1对L毒素与细胞结合的重要性。