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

Cereulide是蜡样芽孢杆菌引起的呕吐型食源性疾病的致病毒素。我们之前的研究表明，它是一种环沉积肽和钾离子载体，并在培养的HEp-2细胞中诱导线粒体肿胀。这种毒素与人类病例中的暴发性肝衰竭有关。化学合成的cereulide与纯化的cereulide具有相同的催吐作用。分别给BALB/c小鼠腹腔注射不同剂量合成或纯化的cereulide，观察其组织病理变化及生理作用。肝细胞出现线粒体异常，如嵴肿胀和缺失。还观察到变性肝细胞中小脂肪滴的剂量依赖性增加。这些小脂肪变性肝细胞分布在中心周围区，并向中间和门静脉周围区扩散。在致死剂量的情况下，肝细胞的大量变性是突出的。这些致死性病变包括大量微脂肪变性和肝细胞凋亡。小鼠其他器官无明显的特异性病理改变。

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.