Cellular mechanism of toxicity of Clostridium perfringens iota-toxin

产气荚膜梭菌iota毒素的细胞毒性机制

• 批准号: 23590526
• 负责人: KOBAYASHI Keiko
• 金额: $ 3.33万
• 依托单位: Tokushima Bunri University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590526/
• 关键词: ウエルシュ菌イオタ毒素; エンドサイトーシス; 初期エンドソーム; リサイクリングエンドソーム; 後期エンドソーム; リソソーム; 結晶化; リサイクリングエンドゾーム

Clostridium perfringens iota-toxin is a binary toxin composed of an enzyme component(Ia) and a binding component(Ib). Each component alone lacks toxic activity, but together they produce cytotoxic effects. This study indicated that an internalized Ia and Ib complex was delivered to early endosomes and that subsequent delivery of Ia to the cytoplasm occured mainly in early endosomes. Then, Ib was transported to late endosomes and lysosomes for degradation. Next, we examined the cytotoxicity of Ib. A431 and A549 cells were susceptible to Ib. Ib bound and formed oligomers in the membranes of A431 cells. Then, Ib caused cell swelling and the rapid depletion of cellular ATP in the cells. Ib also induced permeabilization by propidium iodide without DNA fragmentation in the cells. Ultrastructural studies revealed that A431 cells underwent necrosis after treatment with Ib. We demonstrated that Ib by itself produced cytotoxic activity through necrosis.

产气荚膜梭菌I毒素是由酶组分（Ia）和结合组分（Ib）组成的二元毒素。每种成分单独缺乏毒性活性，但它们一起产生细胞毒性作用。这项研究表明，内化的Ia和Ib复合物被递送到早期内体，随后Ia递送到细胞质主要发生在早期内体中。然后，Ib被转运到晚期内体和溶酶体进行降解。接下来，我们检查了Ib的细胞毒性。A431和A549细胞对Ib敏感。Ib结合并在A431细胞膜中形成寡聚体。然后，Ib引起细胞肿胀和细胞内ATP的快速消耗。Ib还诱导碘化丙啶的透化作用，而细胞中没有DNA片段化。超微结构研究显示，A431细胞在Ib处理后发生坏死。我们证明Ib本身通过坏死产生细胞毒活性。

项目成果

Vizantinによる自然免疫活性化メカニズム

Vizantin的先天免疫激活机制

• 发表时间: 2012
• 作者: 前川純子;倉文明;渡辺祐子;磯部順子;田中忍;中嶋洋;吉野修司;大西真;小田真隆,樽井敬史,亀山直哉,白川大起,屋比久賢太,小林敬子,櫻井純,永浜政博
• 通讯作者: 小田真隆,樽井敬史,亀山直哉,白川大起,屋比久賢太,小林敬子,櫻井純,永浜政博

ウエルシュ菌イオタb成分の細胞毒性機構の解析

产气荚膜梭菌iota b组分的细胞毒性机制分析

• 发表时间: 2012
• 作者: Miyashita A;Iyoda S;Ishii K;Hamamoto H;Sekimizu K;Kaito C;小林敬子,梅崎真理子,小田真隆,櫻井純,永浜政博
• 通讯作者: 小林敬子,梅崎真理子,小田真隆,櫻井純,永浜政博

Intracellular Trafficking of Clostridium perfringens Iota-Toxin b

• DOI: 10.1128/iai.00483-12
• 发表时间: 2012-10-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Nagahama, Masahiro;Umezaki, Mariko;Sakurai, Jun
• 通讯作者: Sakurai, Jun

Clostridium perfringens TpeL Glycosylates the Rac and Ras Subfamily Proteins

• DOI: 10.1128/iai.01019-10
• 发表时间: 2011-02-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Nagahama, Masahiro;Ohkubo, Akiko;Sakurai, Jun
• 通讯作者: Sakurai, Jun

Clostridium perfringens alpha-toxin induces the release of IL-8 through a dual pathway via TrkA in A549 cells.

产气荚膜梭菌 α 毒素通过 A549 细胞中的 TrkA 双重途径诱导 IL-8 的释放。

• DOI: 10.1016/j.bbadis.2012.06.007
• 发表时间: 2012
• 期刊: Biochim. Biophys. Acta
• 作者: Oda M;Shiihara R;Ohmae Y;Kabura M;Takagishi T;Kobayashi K;Nagahama M;Inoue M;Abe T;Setsu K;Sakurai J
• 通讯作者: Sakurai J