First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model.
First Insights Into Within Host Translocation of the Bacillus cereus Toxin Cereulide Using a Porcine Model.
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DOI：
10.3389/fmicb.2018.02652
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发表时间：
2018
影响因子：
5.2
通讯作者：
Ehling-Schulz M
中科院分区：
文献类型：
--
作者：
Bauer T;Sipos W;Stark TD;Käser T;Knecht C;Brunthaler R;Saalmüller A;Hofmann T;Ehling-Schulz M
蜡样芽孢杆菌是一种革兰氏阳性病原体，主要引起两种类型的食源性中毒。腹泻综合症是由肠道生长过程中产生的肠毒素引起的。相反，催吐型是由食物中预先形成的十二肽海藻酸引起的。通常，这两种疾病都是自限性的，但偶尔也会报告更严重的疾病，包括致命的疾病。由于海藻内酯毒素在体内的摄取、转运机制及其毒性作用机制尚不清楚，我们采用猪模型来研究海藻内酯在宿主体内的摄取、排泄途径和分布。使用单剂量 10-150 μg cereulide kg-1 体重对猪进行口服 cereulide 攻击，以研究急性效应，或使用每日剂量 10 μg cereulide kg-1 体重，持续 7 天，以研究长期、慢性暴露的影响。我们的研究表明，部分随食物摄入的海藻酸迅速随粪便排出体外，而部分海藻酸毒素则被吸收、透过细胞膜分布在体内。长期试验的结果表明，雀斑内酯在某些组织和器官中存在生物蓄积，例如肾脏、肝脏、肌肉和脂肪组织。除了在各种组织和器官中检测到外，我们的研究还表明，海藻酸能够穿过血脑屏障，这可能部分解释了人类中毒病例中报告的大脑影响。在我们的猪模型中观察到的神经行为症状，例如癫痫发作和嗜睡，与人类食源性中毒所报告的症状相似。这些症状的迅速出现表明西芹内酯对中枢神经系统（CNS）有直接影响，值得进一步研究。这里提出的猪模型可能有助于详细研究特定的神经生物学效应。此外，我们的研究表明，人类医学中使用的典型诊断标本，例如血液样本和尿液，不适合诊断食源性雀斑肽中毒。相反，通过 SIDA-LC-MS 筛查粪便样本可能是一种简单且非侵入性的方法，用于在临床环境以及食源性疫情爆发的情况下检测海藻酸中毒。
Bacillus cereus is a gram-positive pathogen mainly known to evoke two types of foodborne poisonings. The diarrheal syndrome is caused by enterotoxins produced during growth in the intestine. In contrast, the emetic type is caused by the dodecadepsipeptide cereulide pre-formed in food. Usually, both diseases are self-limiting but occasionally more severe forms, including fatal ones, are reported. Since the mechanisms of cereulide toxin uptake and translocation within the body as well as the mechanism of its toxic action are still unknown, we used a porcine model to investigate the uptake, routes of excretion and distribution of cereulide within the host. Pigs were orally challenged with cereulide using single doses of 10–150 μg cereulide kg-1 body weight to study acute effects or using daily doses of 10 μg cereulide kg-1 body weight administered for 7 days to investigate effects of longtime, chronic exposure. Our study showed that part of cereulide ingested with food is rapidly excreted with feces while part of the cereulide toxin is absorbed, passes through membranes and is distributed within the body. Results from the chronic trial indicate bioaccumulation of cereulide in certain tissues and organs, such as kidney, liver, muscles and fat tissues. Beside its detection in various tissues and organs, our study also demonstrated that cereulide is able to cross the blood–brain–barrier, which may partially explain the cerebral effects reported from human intoxication cases. The neurobehavioral symptoms, such as seizures and lethargy, observed in our porcine model resemble those reported from human food borne intoxications. The rapid onset of these symptoms indicates direct effects of cereulide on the central nervous system (CNS), which warrant further research. The porcine model presented here might be useful to study the specific neurobiological effect in detail. Furthermore, our study revealed that typical diagnostic specimens used in human medicine, such as blood samples and urine, are not suitable for diagnostics of food borne cereulide intoxications. Instead, screening of fecal samples by SIDA-LC-MS may represent a simple and non-invasive method for detection of cereulide intoxications in clinical settings as well as in foodborne outbreak situations.
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影响因子：
5.2
作者：
Ehling-Schulz M;Frenzel E;Gohar M
通讯作者：
Gohar M
DOI：
10.1177/1073858408317955
发表时间：
2008-10
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Fröhlich F;Bazhenov M;Iragui-Madoz V;Sejnowski TJ
通讯作者：
Sejnowski TJ
影响因子：
6.1
作者：
Bauer, Tobias;Stark, Timo;Ehling-Schulz, Monika
通讯作者：
Ehling-Schulz, Monika
影响因子：
4.7
作者：
Girod, V;Dapzol, J;Grélot, L
通讯作者：
Grélot, L
影响因子：
5.1
作者：
Dilkin, P.;Direito, G.;Correa, B.
通讯作者：
Correa, B.