Sjogren R, Neill R, Rachmilewitz D, Fritz D, Newland J, Sharpnack D, Colleton C, Fondacaro J, Gemski P, Boedeker E
Division of Medicine, Walter Reed Army Institute of Research, Washington, D.C.
Gastroenterology. 1994 Feb;106(2):306-17. doi: 10.1016/0016-5085(94)90587-8.
BACKGROUND/AIMS: Enteroadherent Escherichia coli that produce Shiga-like toxins are important causes of human disease, including enterohemorrhagic E. coli-induced colitis (EHEC). The role of Shiga-like toxins in these illnesses is unclear. The aim of this study was to establish an animal model for human EHEC and to determine the role of Shiga-like toxin I (SLT-I) in this model.
E. coli strain RDEC-1 is an enteroadherent rabbit diarrheal pathogen. An isogenic variant of RDEC-1 (termed RDEC-H19A) producing high levels of SLT-I was obtained by infecting RDEC-1 with an SLT-I-converting bacteriophage. The effects of in vivo enteric infection produced in rabbits by RDEC-H19A were compared with those in uninfected and RDEC-1-infected animals.
SLT-I-producing RDEC-H19A induced a severe, noninvasive, enteroadherent infection in rabbits. Clinically, infection with RDEC-H19A was more severe than infection with RDEC-1 and caused more serious histological lesions including vascular changes, edema, and more severe inflammation. Interleukin 1 and platelet-activating factor appear to be important inflammatory mediators to this infection.
The illness induced by RDEC-H19A in rabbits resembled enterohemorrhagic E. coli-induced colitis of humans. SLT-I is an important virulence factor in the pathogenesis of EHEC.
背景/目的:产生志贺样毒素的肠黏附性大肠杆菌是人类疾病的重要病因,包括肠出血性大肠杆菌引起的结肠炎(EHEC)。志贺样毒素在这些疾病中的作用尚不清楚。本研究的目的是建立人类EHEC的动物模型,并确定志贺样毒素I(SLT-I)在该模型中的作用。
大肠杆菌菌株RDEC-1是一种肠黏附性兔腹泻病原体。通过用SLT-I转化噬菌体感染RDEC-1,获得了产生高水平SLT-I的RDEC-1同基因变体(称为RDEC-H19A)。将RDEC-H19A在兔体内引起的肠道感染效应与未感染和RDEC-1感染动物的效应进行比较。
产生SLT-I的RDEC-H19A在兔中引起严重的、非侵袭性的、肠黏附性感染。临床上,RDEC-H19A感染比RDEC-1感染更严重,并导致更严重的组织学病变,包括血管变化、水肿和更严重的炎症。白细胞介素1和血小板活化因子似乎是这种感染的重要炎症介质。
RDEC-H19A在兔中引起的疾病类似于人类肠出血性大肠杆菌引起的结肠炎。SLT-I是EHEC发病机制中的重要毒力因子。