Development of a mouse model of Hemolytic Uremic Syndrome (HUS) by oral inoculation with Shiga toxin-producing (Stx) Escherichia coli (STEC)

R. J. FERNÁNDEZ BRANDO; L. V. BENTANCOR; M. V. RAMOS; G. C. FERNANDEZ; E. MILEWIBSKY; R. MEISS; M. RIVAS; M. S. PALERMO

Rio de Janeiro

Congreso; 13th International Congress of Immunology; 2007

International Union of Immunological Societies

Because HUS mouse model by intravenous-Stx2 injection does not allow to study early stage of disease, we aimed to establish an intragastrically infected mouse model. Since adult mouse are resistant to infection, we inoculated immature weaned mouse (16-19 days old) with different STEC isolated from HUS-patients (125/99;119/01;108/01;431/01) and two strains do not producing Stx, isolated from diarrheal patients (893/05 and 605/03) (control strains). We evaluated mortality, urea level in serum, number of viable STEC isolated from stools and gut, PCR-detection of stx2 in these STEC, and histopathology. The optimal inoculum dose by mouse was 5x107 CFU. Between STEC strains, the most pathogenic was the 125/99, given a mortality rate of  53% and urea level of 137±26 mg%, 72h post-infection (n=30). The renal damage was confirmed histopathologically. On the other hand, the mortality rate with control strains were 17% (893/05) and 12.5% (605/03) with uremia of 58±4 (n=18) and 44±3 (n=12) respectively. There was a significant difference in mortality and uremia values between mice inoculated with control and STEC strains (p<0.01). While strain 125/99 was recovered from stools (7/9 mice), small intestine (7/9) and large intestine (4/9) up to 48h postinoculation, the control strain 605/03 only was recovered from stool (2/6). STEC strains were confirmed by PCR. In addition, all moribund mice had viable STEC and Stx2 faecal shedding at 72h postinoculation. We concluded that immature weaned mice show Stx-renal damage after intragastrically STEC inoculation being a good model to study early stages of HUS.