Biological activity and biosynthetic mechanism of an emetic toxin produced by Bacillus cereus

蜡状芽孢杆菌催吐毒素的生物活性及生物合成机制

• 批准号: 08457086
• 负责人: OHTA Michio
• 金额: $ 4.29万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457086/
• 关键词: cereulide; Bacillus cereus; foodborne illness; toxin; ionophore; liver failure; apotosis; mitochondria; cereulide; 脂肪変性; K^+ イオノフォア

Cereulide is the causative toxin of the emetic type foodborne illness caused by Bacillus cereus. Our previous studies exhibited that it is a cyclic depsipeptide and a potassium ionophore and that it induces mitochondrial swelling in cultured HEp-2 cells. This toxin was associated with fulminant liver failure in a human case. Chemically synthesized cereulide had the same emetic effect as purified cereulide. BALB/c mice were i.p. injected with various dosed of synthetic or purified cereulide and the development of histopathological changes as well as physiological effects were examined. Hepatocytes showed the abnormality of the mitochondria such as swelling and loss of cristae. Dose-dependent increase of small fatty droplets in the degenerated hepatocytes was also observed. These microsteatotic hepatocytes were distributed in the pericentral area and spread to the intermediate and periportal areas. In the cases of lethal doses, massive degeneration of hepatocytes was prominent. These fatal lesions included massive microsteatosis and apotosis of hepatocytes. Other organs of these mice had no apparent specific pathological changes.

蜡样内酯是由蜡状芽孢杆菌引起的呕吐型食源性疾病的致病毒素。我们以前的研究表明，它是一种环状脱脂肽和钾离子载体，并能诱导培养的Hep-2细胞线粒体肿胀。在一例人类病例中，这种毒素与暴发性肝衰竭有关。化学合成的麦粒内酯与纯化的麦粒内酯具有相同的催吐作用。BALB/c小鼠ip。注射不同剂量的人工合成或纯化的谷氨酰胺，观察其组织病理学变化及生理效应。肝细胞表现为线粒体肿胀、嵴消失等异常改变。变性肝细胞中的小脂肪滴也呈剂量依赖性增加。这些微小的脂肪变性肝细胞分布在中心区周围，并向中间和门静脉周围扩散。在致死剂量的情况下，肝细胞大量变性明显。这些致命性病变包括大量微脂肪变性和肝细胞凋亡。小鼠其他脏器未见明显的特异性病变。

项目成果

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