Animal Models for STEC-Mediated Disease

互联网2014-02-13

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Escherichia coli O157:H7 is the most common infectious cause of bloody diarrhea or hemorrhagic colitis (HC) in the United States (1 ). The potentially serious nature of infection with E. coli O157:H7 is illustrated by the fact that about 6% of those infected individuals (particularly children) develop a sequela called the hemolytic uremic syndrome or HUS (2 ). The HUS is characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure, central nervous system involvement, and, in 3–5% of children, death (reviewed in ref. 3 ). E. coli O157:H7 belongs to a subset of Shiga toxin-producing E. coli (STEC) named enterohemorrhagic E. coli (or EHEC) that not only make Shiga toxins (Stxs, formerly called Shiga-like toxins and alternatively known as verotoxins) but also attach to the bowel by a protein called intimin and evoke an attach and efface (A/E) lesion at the site of the bacterial-enterocyte interface (4 ). The pathogenic process by which E. coli O157:H7 and some other STEC evoke blood in the stools and cause the HUS and the adult version of HUS, thrombotic thrombocytopenic purpura (TTP), remains incompletely understood. Nevertheless, Stx appears to play a pivotal role in these manifestations, and endothelial cells are a primary target of Stx action (5 ,6 ). A number of animal species have been tried as models of STEC infection or Stx-mediated disease. However, in no single animal system is there replication of the entire spectrum of the infectious disease process as observed in humans (i.e., in humans, the steps in STEC pathogenesis include oral infection followed by diarrhea, sometimes HC, and occasionally the HUS). Nevertheless, there are animal models that mimic parts of the disease process. These models are described in the following subheadings, with the exception of pig and bovine models, which are described elsewhere in this volume. A summary of the animal types, treatments, and outcomes is given in Table 1 .

Table 1 Summary of Animal Models, Treatments and Outcomes

Animal type	Animal strain	Treatment(s)	Route of inoculation	Outcome or symptoms
Mouse	CD-I, DBA/2J	str/most O157 strains	Oral feeding	Colonization
	CD-I	str/some Stx2 producers, Stx2d producers	Oral feeding	Renal damage, death
	ICR	str/mitomycin C/STEC strain E32511/HSC	Intragastric feeding	Encephalopathy
	CD-I	str/ciprofloxacin/STEC strain 1:361R	Intragastric feeding	Death
	C3H/HeN	STEC strain 86-24	Intragastric feeding	Loose stool, mesangial matrix expansion
	C57BL/6	Low-protein diet/STEC strain N-9	Intragastric feeding	Neurologic and systemic manifestations, cerebral hemorrhages, death
Rabbit	New Zealand white	STEC strain UC741	Intragastric feeding	Diarrhea, death
	New Zealand white	RDEC-H19A	Intragastric feeding	Diarrhea, colonic subserosal hemorrhages and submucosal edema and vascular changes
	New Zealand white, infant	Stxl	Intragastric	Diarrhea, mucosal damage in the colon, some death
	New Zealand white	Stxl	Injection into marginal ear vein	Some diarrhea, CNS symptoms, cecal mucosal edema and submucosal vascular changes in some animals
	Japanese white rabbits	Stx2	Injection into marginal ear vein	Hemorrhagic diarrhea, flaccid paresis, convulsions
	Not stated in chapter	Stx2	Continuous pump in peritoneum	Diarrhea and intestinal lesions similar to HC
Chicken		0157 STEC strains	Intragastric feeding	Colonization, A/E lesions
Dog	Greyhound	Stxl or Stx2	Injection	Thrombocytopenia, anemia, HC
Baboon	Papio c. cynocephalus or Papio c. anubis or	Stxl	Injection into cephalic vein	Damage to gastrointestinal mucusa, renal failure, thrombocytopenia, other HUS signs

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