Garcia Alexis, Bosques Carlos J, Wishnok John S, Feng Yan, Karalius Brad J, Butterton Joan R, Schauer David B, Rogers Arlin B, Fox James G
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge 02139, USA.
J Infect Dis. 2006 Apr 15;193(8):1125-34. doi: 10.1086/501364. Epub 2006 Mar 6.
Enterohemorrhagic Escherichia coli (EHEC) produces Shiga toxin (Stx) and causes renal disease in humans. Dutch Belted (DB) rabbits naturally infected with EHEC O153 develop hemolytic-uremic syndrome-like disease. The aims of this study were to experimentally reproduce O153-induced renal disease in DB rabbits and investigate bacterial and host factors involved in pathogenesis. The pathogenicity of E. coli O157:H7 was also investigated in rabbits. The stx1AB region of O153 was sequenced. By use of liquid chromatography-tandem mass spectrometry, we identified homologs of the Stx receptor, globotriaosylceramide (Gb3), in rabbit kidney extracts. Infected rabbits developed clinical signs and intestinal and kidney lesions. Renal pathological changes consisted of intimal swelling, perivascular edema, erythrocyte fragmentation, capillary thickening, luminal constriction, leukocytic infiltration, mesangial deposits, and changes in Bowman's capsule and space. Sequence analysis of a approximately 7-kb region of the O153 chromosome indicated homology to the Stx1-producing bacteriophage H19B. Our findings indicate that DB rabbits are suitable for the study of the renal manifestations of EHEC infection in humans.
肠出血性大肠杆菌（EHEC）产生志贺毒素（Stx）并可导致人类肾病。自然感染EHEC O153的荷兰带兔（DB兔）会发展出溶血尿毒综合征样疾病。本研究的目的是在DB兔中通过实验再现O153诱导的肾病，并研究发病机制中涉及的细菌和宿主因素。还在兔中研究了大肠杆菌O157:H7的致病性。对O153的stx1AB区域进行了测序。通过液相色谱-串联质谱法，我们在兔肾提取物中鉴定出了Stx受体——球三糖神经酰胺（Gb3）的同源物。受感染的兔子出现了临床症状以及肠道和肾脏病变。肾脏病理变化包括内膜肿胀、血管周围水肿、红细胞破碎、毛细血管增厚、管腔狭窄、白细胞浸润、系膜沉积以及鲍曼囊和肾小囊间隙的变化。对O15染色体约7kb区域的序列分析表明其与产生Stx1的噬菌体H19B具有同源性。我们的研究结果表明，DB兔适用于研究人类EHEC感染的肾脏表现。
