Lünse Christina E, Mayer Günter
Life and Medical Sciences Institute, University of Bonn, Gerhard-Domagk-Str. 1, Bonn, 53121, Germany.
Department of Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT, 06520-8103, USA.
Methods Mol Biol. 2017;1520:227-235. doi: 10.1007/978-1-4939-6634-9_13.
With the rise of multidrug resistant bacteria and a growing number of nosocomial infections, there has been an increased interest in finding new antibacterial drugs and drug targets. Riboswitches represent attractive new antibacterial drug targets, because they not only inherently recognize a specific metabolite or ion with their RNA aptamer domain, but also often regulate essential metabolic pathways. Here, we describe a reporter gene-based screen to identify compounds that activate the thiamine pyrophosphate (TPP) riboswitch in bacteria. This assay can be easily adapted for different riboswitch classes and thus has the potential to target many essential metabolic pathways and a broad spectrum of bacterial pathogens.
随着多重耐药细菌的增加以及医院感染数量的不断上升，人们对寻找新的抗菌药物和药物靶点的兴趣日益浓厚。核糖开关是颇具吸引力的新型抗菌药物靶点，因为它们不仅能通过其RNA适体结构域固有地识别特定代谢物或离子，还常常调控基本代谢途径。在此，我们描述了一种基于报告基因的筛选方法，用于鉴定激活细菌中硫胺焦磷酸（TPP）核糖开关的化合物。该检测方法可轻松适用于不同类型的核糖开关，因此有潜力针对许多基本代谢途径和广泛的细菌病原体。
