Open AccessIdentification of Antibiotics That Diminish Disease in a Murine Model of Enterohemorrhagic Escherichia coli Infection
Author(s) -
Sabrina Mühlen,
Isabell Ramming,
Marina C. Pils,
Martin B. Koeppel,
Jana Glaser,
John M. Leong,
Antje Flieger,
Bärbel Stecher,
Petra Dersch
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02159-19
Subject(s) - escherichia coli , antibiotics , microbiology and biotechnology , shiga toxin , diarrhea , biology , disease , virology , medicine , gene , biochemistry
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 ϕ stx 2dact mouse model and show that stx 2d -inducing antibiotics resulted in weight loss and kidney damage despite clearance of the infection. However, several non-Stx-inducing antibiotics cleared bacterial infection without causing Stx-mediated pathology. Our results suggest that these antibiotics might be useful in the treatment of EHEC-infected human patients and decrease the risk of HUS development.