ROLE OF SHIGA TOXIN IN THE PATHOGENESIS OF BACILLARY DYSENTERY, STUDIED BY USING A TOX- MUTANT OF SHIGELLA-DYSENTERIAE-1
ROLE OF SHIGA TOXIN IN THE PATHOGENESIS OF BACILLARY DYSENTERY, STUDIED BY USING A TOX- MUTANT OF SHIGELLA-DYSENTERIAE-1
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DOI：
10.1128/iai.56.12.3099-3109.1988
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发表时间：
1988-12-01
影响因子：
3.1
通讯作者：
SANSONETTI, PJ
中科院分区：
文献类型：
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作者：
FONTAINE, A;ARONDEL, J;SANSONETTI, PJ
志贺氏痢疾杆菌1型毒理突变株。SC501是通过克隆志贺毒素操纵子，在a亚基基因中插入一个卡带，并在体外与野生型基因交换突变序列而进行基因工程改造的。SC501产生少量残留细胞毒性，不能被针对志贺毒素的兔免疫血清中和。对培养细胞的侵染表明志贺毒素对细菌的胞内生长速率和侵染宿主细胞的快速杀伤没有影响。另一方面，在猕猴体内感染野生型菌株或突变型菌株时，观察到一些显著的差异。入侵菌株产生志贺毒素与粪便中血液的存在、血液多形核细胞的急剧下降和组织病理学改变有关，如结肠粘膜结缔组织内毛细血管的破坏、腹膜间皮的严重炎性血管炎和炎症细胞向肠腔的大量外排。我们认为志贺毒素通过诱导结肠血管损伤来影响细菌性痢疾的严重程度，导致感染过程中出现血便、肠缺血和多形核肠室膨胀。
A Tox- mutant of Shigellla dysenteria 1. SC501, was genetically engineered by cloning the Shiga toxin operon, inserting a cassette into the A subunit gene, and exchanging this in vitro-mutagenized sequence with the wild-type gene. SC501 produced a low amount of residual cytotoxicity which was not neutralized by a rabbit immune serum directed against Shiga toxin. Invasion of cultured cells demonstrated that Shiga toxin had no effect on the rate of intracellular growth of bacteria or on the rapid killing of invaded host cells. On the other hand, several significant differences were observed in macaque monkeys infected intragastrically with either the wild-type strain or its mutant. The production of Shiga toxin by the invading strain was correlated with the presence of blood within stools, a sharp drop in blood polymorphonuclear cells, and histopathological alterations, such as the destruction of capillary vessels within the connective tissue of the colonic mucosa, severe inflammtory vasculitis of the peritoneal mesothelium, and major efflux of inflammatory cells to the intestinal lumen. It is proposed that Shiga toxin influences the severity of bacillary dysentery by inducing colonic vascular damage, which accounts for bloody stools, intestinal ischemia, and inflation of a polymorphonuclear intestinal compartment during the infectious process.