Mühlen Sabrina, Ramming Isabell, Pils Marina C, Koeppel Martin, Glaser Jana, Leong John, Flieger Antje, Stecher Bärbel, Dersch Petra
Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Institute for Infectiology, University of Münster, Münster, Germany.
Antimicrob Agents Chemother. 2020 Mar 24;64(4). doi: 10.1128/AAC.02159-19.
Infections with enterohemorrhagic (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 expression. Here, we systematically tested different classes of antibiotics and found that their influence on expression and release varies significantly. We assessed a selection of these antibiotics using the ϕ mouse model and show that -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.
肠出血性大肠杆菌（EHEC）感染可导致从轻度腹泻到溶血尿毒综合征（HUS）等疾病，并且是高收入国家儿童肾衰竭的最常见原因。该疾病的严重程度源于志贺毒素（Stx）的释放。通常避免使用抗生素治疗EHEC感染，因为这可能导致其表达增加。在此，我们系统地测试了不同类别的抗生素，发现它们对其表达和释放的影响差异显著。我们使用ϕ小鼠模型评估了这些抗生素中的一部分，结果表明，诱导Stx的抗生素尽管清除了感染，但会导致体重减轻和肾脏损伤。然而，几种不诱导Stx的抗生素清除了细菌感染，且未引起Stx介导的病理变化。我们的结果表明，这些抗生素可能对治疗EHEC感染的人类患者有用，并降低HUS发生风险。
