COMPARISON OF THE RELATIVE TOXICITIES OF SHIGA-LIKE TOXINS TYPE-I AND TYPE-II FOR MICE
COMPARISON OF THE RELATIVE TOXICITIES OF SHIGA-LIKE TOXINS TYPE-I AND TYPE-II FOR MICE
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DOI：
10.1128/iai.61.8.3392-3402.1993
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发表时间：
1993-08-01
影响因子：
3.1
通讯作者：
SAMUEL, JE
中科院分区：
文献类型：
--
作者：
TESH, VL;BURRIS, JA;SAMUEL, JE
在早期使用链霉素处理的肠出血性大肠杆菌（EHEC）感染小鼠模型的研究中，喂食产生志贺样毒素II型（SLT-II）菌株的动物发生急性肾皮质坏死并死亡，而喂食产生志贺样毒素I型（SLT-I）克隆的小鼠没有死亡（E. A.瓦多尔科夫斯基湖M. Sung，J. A. Burris，J.E. Samuel和A. D.奥布莱恩，感染。Immun. 58：3959-3965，1990）。为了检查我们在小鼠感染模型中注意到的两种毒素之间差异的基础，我们向小鼠注射了纯化的毒素并进行了组织病理学检查。尽管这两种毒素之间的遗传和结构相似，但当静脉内或腹腔内注射到小鼠中时，SLT-II具有比SLT-I低约400倍的50%致死剂量（LD 50）。毒素注射小鼠的组织学检查显示，可检测到的损害仅限于肾皮质小管上皮细胞。被动给予抗SLT-II抗体可保护小鼠免受SLT-II介导的肾损伤和死亡。免疫荧光染色的正常小鼠肾脏切片与纯化的SLT-Ⅰ或SLT-Ⅱ孵育表明，这两种毒素结合皮质小管和髓管上皮细胞。与SLT-I相比，SLT-II具有更好的热稳定性和pH稳定性，表明SLT-II是一种相对更稳定的大分子。虽然这两种毒素结合globotriaosylceramide，在固相结合试验中，结合与更高的亲和力。未检测到两种毒素之间的酶活性差异。这些数据表明，两种毒素之间的结构/功能差异，可能涉及全毒素稳定性和/或受体亲和力，可能有助于小鼠中的LD 50差异。
In earlier studies using a streptomycin-treated mouse model of infection caused by enterobemorrhagic Escherichia coli (EHEC), animals fed Shiga-like toxin type II (SLT-II)-producing strains developed acute renal cortical necrosis and died, while mice fed Shiga-like toxin type I (SLT-I)-producing clones did not die (E. A. Wadolkowski, L. M. Sung, J. A. Burris, J. E. Samuel, and A. D. O'Brien, Infect. Immun. 58:3959-3965, 1990). To examine the bases for the differences we noted between the two toxins in the murine infection model, we injected mice with purified toxins and carried out histopathological examinations. Despite the genetic and structural similarities between the two toxins, SLT-II had a 50% lethal dose (LD50) which was approximately 400 times lower than that of SLT-I when injected intravenously or intraperitoneally into mice. Histopathologic examination of toxin-injected mice revealed that detectable damage was limited to renal cortical tubule epithelial cells. Passive administration of anti-SLT-II antibodies protected mice from SLT-II-mediated kidney damage and death. Immunofluorescence staining of normal murine kidney sections incubated with purified SLT-I or SLT-II demonstrated that both toxins bound to cortical tubule and medullary duct epithelial cells. Compared with SLT-I, SLT-II was more heat and pH stable, suggesting that SLT-II is a relatively more stable macromolecule. Although both toxins bound to globotriaosylceramide, SLT-1 bound with a higher affinity in a solid-phase binding assay. Differences in enzymatic activity between the two toxins were not detected. These data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice.