Kim Sang-Hyun, Lee Yong-Hoon, Lee Sang-Ho, Lee Sang-Rae, Huh Jae-Won, Kim Sun-Uk, Chang Kyu-Tae
The National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongwon, Chungbuk, Korea.
FEMS Immunol Med Microbiol. 2011 Dec;63(3):427-34. doi: 10.1111/j.1574-695X.2011.00869.x. Epub 2011 Oct 4.
Hemolytic uremic syndrome (HUS) is characterized by acute renal failure in children and is typically complicated with thrombocytopenia and hemolytic anemia. Although mouse models of HUS have been evaluated using Shiga toxin (STx) combined with or without lipopolysaccharide (LPS), no HUS model has been tested using purified outer membrane vesicles (OMVs) from STx-producing Escherichia coli (STEC) O157:H7. Accordingly, we investigated whether OMVs of STEC O157:H7 conveying STx2 and LPS can cause HUS-like symptoms in mice inoculated intraperitoneally. Three types of OMVs differing in LPS acylation status and STx2 amount were used to compare their ability to induce HUS-like symptoms. Native OMVs (nOMV) with fully hexa-acylated LPS caused HUS-like symptoms at 72-96 h after dually divided injections of 1 μg nOMV per animal. However, elevated doses of modified OMVs (mOMV) carrying mainly penta-acylated LPS were required to induce similar HUS signs. Moreover, mitomycin-C-induced OMVs (mcOMV) that were enriched with STx2 induced HUS-like symptoms similar to those of nOMV at the same dose. These results suggest that the OMVs of STEC O157:H7 potentiated with STx2 and fully hexa-acylated LPS can be utilized for inducing HUS-like symptoms in mice and could be the causative material involved in the development of HUS.
溶血尿毒综合征（HUS）的特征是儿童急性肾衰竭，通常伴有血小板减少和溶血性贫血。尽管已使用志贺毒素（STx）联合或不联合脂多糖（LPS）对HUS小鼠模型进行了评估，但尚未使用产志贺毒素大肠杆菌（STEC）O157:H7的纯化外膜囊泡（OMV）测试过HUS模型。因此，我们研究了携带STx2和LPS的STEC O157:H7的OMV是否能在腹腔注射的小鼠中引起类似HUS的症状。使用三种LPS酰化状态和STx2含量不同的OMV来比较它们诱导类似HUS症状的能力。具有完全六酰化LPS的天然OMV（nOMV）在每只动物分两次注射1μg nOMV后72 - 96小时引起类似HUS的症状。然而，需要更高剂量的主要携带五酰化LPS的修饰OMV（mOMV）来诱导类似的HUS体征。此外，富含STx2的丝裂霉素C诱导的OMV（mcOMV）在相同剂量下诱导出与nOMV类似的HUS样症状。这些结果表明，用STx2和完全六酰化LPS增强的STEC O157:H7的OMV可用于在小鼠中诱导类似HUS的症状，并且可能是参与HUS发病的致病物质。
