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志贺毒素及其他细胞毒素与志贺氏菌病神经学表现的关联。

The association of Shiga toxin and other cytotoxins with the neurologic manifestations of shigellosis.

作者信息

Ashkenazi S, Cleary K R, Pickering L K, Murray B E, Cleary T G

机构信息

Department of Pediatrics, University of Texas Medical School, Houston 77030.

出版信息

J Infect Dis. 1990 May;161(5):961-5. doi: 10.1093/infdis/161.5.961.

DOI:10.1093/infdis/161.5.961
PMID:2324546
Abstract

The neurologic symptoms in human shigellosis have often been attributed to Shiga toxin, although its exact role has not been determined. By use of a [3H] thymidine-labeled HeLa cell assay, cytotoxic activity was demonstrated in stool but not cerebrospinal fluid or serum from five patients with shigellosis presenting with seizures or encephalopathy. Bacterial isolates produced 16.0-88.2 CD50 (50% cytotoxic dose) of cytotoxin/mg of protein. The toxin activity in stool and the cytotoxic activity of the isolates were not neutralized by antiserum to purified Shiga toxin. DNA hybridization studies showed that Shigella isolates from these patients lacked the structural genes for Shiga toxin. The cytotoxin produced was also distinct from Shiga-like toxins I and II. Sonicates of the Shigella strains injected intraperitoneally into mice caused lethargy and lethality. The toxin activity was heat-labile and sensitive to trypsin, indicating that its active component is protein. Ultrafiltration and gel filtration chromatography showed a molecular mass of 100-125 kDa. Thus Shiga toxin production is not essential for the development of neurologic manifestations of shigellosis; other toxic products may play a role.

摘要

人类志贺氏菌病的神经症状常被归因于志贺毒素,尽管其确切作用尚未确定。通过使用[3H]胸苷标记的HeLa细胞检测法,在5例出现癫痫或脑病的志贺氏菌病患者的粪便中检测到细胞毒性活性,但在脑脊液或血清中未检测到。细菌分离株产生的细胞毒素为16.0 - 88.2 CD50(50%细胞毒性剂量)/毫克蛋白质。粪便中的毒素活性和分离株的细胞毒性活性未被抗纯化志贺毒素的抗血清中和。DNA杂交研究表明,这些患者的志贺氏菌分离株缺乏志贺毒素的结构基因。所产生的细胞毒素也与类志贺毒素I和II不同。将志贺氏菌菌株的超声裂解物腹腔注射到小鼠体内会导致嗜睡和死亡。毒素活性对热不稳定且对胰蛋白酶敏感,表明其活性成分是蛋白质。超滤和凝胶过滤色谱显示分子量为100 - 125 kDa。因此,志贺毒素的产生对于志贺氏菌病神经表现的发展并非必不可少;其他有毒产物可能起作用。

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