Identification of antibiotics that diminish disease in a murine model of enterohemorrhagic infection.

Abstract

Infections with enterohemorrhagic Escherichia coli (EHEC) cause disease ranging from mild diarrhea to hemolytic uremic syndrome (HUS) and are the most common cause of renal failure in children in high income countries. The severity of the disease derives from the release of Shiga toxins (Stx). The use of antibiotics to treat EHEC infections is generally avoided as it can result in increased stx expression. Here, we systematically tested different classes of antibiotics and found that their influence on stx expression and release varies significantly. We assessed a selection of these antibiotics in vivo using the Citrobacter rodentium φstx2dact mouse model and show that stx2d-inducing antibiotics resulted in weight loss and kidney damage despite clearing the infection. However, several non-Stx-inducing antibiotics cleared bacterial infection without causing Stx-mediated pathology. Our results suggest that these antibiotics could be useful in the treatment of EHEC-infected human patients and decrease the risk of HUS development.