Renal damage and death in weaned mice after oral infection with Shiga toxin 2‐producing Escherichia coli strains

• Published in: Clinical and experimental immunology Vol. 153; no. 2; pp. 297 - 306
• Main Authors: Brando, R. J. F., Miliwebsky, E., Bentancor, L., Deza, N., Baschkier, A., Ramos, M. V., Fernández, G. C., Meiss, R., Rivas, M., Palermo, M. S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2008; Blackwell; Blackwell Science Inc
• Subjects: Age Factors; Analytical, structural and metabolic biochemistry; Animal Studies; Animals; Biological and medical sciences; Diarrhea - microbiology; Diarrhea - mortality; Escherichia coli; Female; Foodborne Diseases - microbiology; Foodborne Diseases - mortality; Foodborne Diseases - pathology; Fundamental and applied biological sciences. Psychology; Hematologic and hematopoietic diseases; Hemolytic-Uremic Syndrome - microbiology; Hemolytic-Uremic Syndrome - mortality; Hemolytic-Uremic Syndrome - pathology; HUS mouse model; Intestines - microbiology; Intestines - pathology; Kidney - pathology; Malnutrition; Medical sciences; Mice; Mice, Inbred BALB C; Models, Animal; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; oral infection; Platelet diseases and coagulopathies; renal damage; Renal failure; Shiga Toxin 2; Shiga-Toxigenic Escherichia coli - pathogenicity; Stx2; Survival Rate; Weaning; Escherichia coli; Hemopathy; Biochemistry; oral infection; Kidney; renal damage; Hemolytic anemia; Bacteria; Stx2; Enterobacteriaceae; Kidney disease; Thrombocytopenia; HUS mouse model; Urinary system disease; Hemolytic uremic syndrome; Acute; Rodentia; Oral administration; Infection; Toxin; Vertebrata; Platelet; Mammalia; Urinary system; Mouse; Animal; Renal failure; Death; Models
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2008.03698.x

Summary
Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infections are considered a public health problem in both developed and developing countries because of their increasing incidence and the severity of clinical presentation. Approximately 10% of infected patients develop complications such as haemolytic uraemic syndrome (HUS) characterized by acute renal failure, thrombocytopenia and haemolytic anaemia. The precise sequence of events leading to HUS is still understood incompletely. Because of the lack of a reproducible small animal model for EHEC infections, in vivo studies examining EHEC–host early interactions are limited and insufficient. The aim of this study was to characterize the weaned BALB/c mouse as a model of E. coli O157:H7 infection. In this paper we report that human Shiga toxin 2 (Stx2)‐producing EHEC strains can adhere to the intestinal epithelium of weaned BALB/c mice, and produce local damage which leads to systemic disease and death in a percentage of infected mice. The lethality of the EHEC strain is closely age‐dependent, and is related to the bacterial ability to colonize intestine and to produce Stx2. It can be concluded that the weaned BALB/c mouse can be used as a small animal model to study host early responses, and the role of bacterial pathogenic factors in the induction of systemic disease, thus providing a useful tool for the evaluation of therapeutic or vaccine approaches.