Pathogenesis of Colitis in Germ-Free Mice Infected With EHEC O157:H7.
Pathogenesis of Colitis in Germ-Free Mice Infected With EHEC O157:H7.
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DOI：
10.1177/0300985817691582
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发表时间：
2017-07
影响因子：
2.4
通讯作者：
Alteri CJ
中科院分区：
文献类型：
--
作者：
Eaton KA;Fontaine C;Friedman DI;Conti N;Alteri CJ
肠出血性大肠杆菌（EHEC）是大肠杆菌的一种。表达滋贺毒素（Stx）并引起出血性结肠炎的大肠杆菌。在某些情况下，疾病可能进展为溶血性尿毒症综合征，这是一种潜在的致命性肾脏疾病。肠道和肾脏疾病都与stx基因的表达有关，这些基因通常携带在溶原性噬菌体上。毒素在噬菌体诱导和转化为裂解性生长后表达。作者先前使用无菌小鼠模型来证明毒素基因表达在体内生长期间增强，并且肾脏疾病依赖于原噬菌体诱导和Stx2表达。在目前的研究中，作者记录和量化坏死性结肠炎，检查肠道和肾脏疾病的进展，并确定Stx 2，噬菌体基因和3型分泌系统（T3SS）在细菌定植和结肠炎和全身性疾病中的作用。接种后1天，EHEC单克隆小鼠发生结肠炎，此后严重程度降低。随后发生全身性疾病。感染EHEC突变株显示，肾功能衰竭和脾坏死是绝对依赖于Stx2的表达，但T3SS功能和原噬菌体切除是不必要的全身性疾病。相反，结肠炎仅部分依赖于Stx2。这项研究表明，在无菌小鼠中，与人类患者一样，EHEC导致早期结肠炎，随后是肾衰竭，并且全身性疾病而不是结肠炎是Stx2依赖的。
Enterohemorrhagic Escherichia coli (EHEC) are strains of E. coli that express Shiga toxins (Stx) and cause hemorrhagic colitis. In some cases, disease can progress to hemolytic uremic syndrome, a potentially fatal form of kidney disease. Both enteric and renal disease are associated with the expression of stx genes, which are often carried on lysogenic phage. Toxin is expressed following induction and conversion of the phage to lytic growth. The authors previously used a germ-free mouse model to demonstrate that toxin gene expression is enhanced during growth in vivo and that renal disease is dependent on both prophage induction and expression of Stx2. In the current study, the authors document and quantify necrotizing colitis, examine the progression of enteric and renal disease, and determine the role of Stx2, phage genes, and the type 3 secretion system (T3SS) in bacterial colonization and colitis and systemic disease. By 1 day after inoculation, EHEC-monocolonized mice developed colitis, which decreased in severity thereafter. Systemic disease developed subsequently. Infection with EHEC mutant strains revealed that renal failure and splenic necrosis were absolutely dependent on the expression of Stx2 but that T3SS function and prophage excision were not necessary for systemic disease. In contrast, colitis was only partly dependent on Stx2. This study demonstrates that in germ-free mice, like in human patients, EHEC causes early colitis followed by renal failure and that systemic disease but not colitis is Stx2 dependent.