Title:Development of a Mouse Model of Shiga Toxin 2 (Stx2) Intoxication for Testing Therapeutic Agents Against Hemolytic Uremic Syndrome (HUS)
Volume: 22
Issue: 34
Author(s): Maria Pilar Mejias, Romina Jimena Fernandez-Brando, Maria Victoria Ramos, Maria Jimena Abrey-Recalde, Elsa Zotta, Roberto Meiss and Marina Sandra Palermo
Affiliation:
Keywords:
Shiga toxin, mouse model, neutralizing antibodies, HUS, STEC, therapy.
Abstract: Background: Hemolytic Uremic Syndrome (HUS) caused by infections with
Shiga toxin (Stx)-producing E. coli is a life-threatening complication characterized by acute
renal failure, thrombocytopenia and hemolytic anemia. Stx is the main pathogenic factor.
Therefore, the mouse model by intravenous administration of a single lethal dose of Stx is
often used to explore its pathogenic mechanisms.
Objective: The aim of this work was to develop an alternative mouse model of Stx type 2
(Stx2) intoxication to evaluate new therapeutic strategies.
Methods and Results: One lethal dose of Stx2 was divided in four daily doses. We observed
a dose-dependent toxicity characterized by neutrophilia, leukocytopenia and renal damage.
Most importantly, we demonstrated that the polyclonal anti-Stx2 serum was able to protect
mice from fatal evolution even when administered together the third dose of Stx2.
Conclusion: This model would provide an advantage for evaluation of therapeutic strategies.
Furthermore, the results presented herein suggest that appropriate treatment with anti-Stx2 agents following the
appearance of initial clinical signs may block the ongoing outcome or may alleviate disease in patients who have
just been diagnosed with HUS. However, the delay in the onset of therapy would be unsafe.
