Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Microbes Infect. 2009 Dec;11(14-15):1097-105. doi: 10.1016/j.micinf.2009.08.002. Epub 2009 Aug 7.
The probiotic bacterium Escherichia coli Nissle 1917 (EcN) constitutes a prospective vector for delivering heterologous therapeutic molecules to treat several human disorders. To add versatility to this carrier system, bacteria should be equipped with expression modules that can be regulated deliberately in a temporal and quantitative manner. This approach is called in vivo remote control (IVRC) of bacterial vectors. Here, we have evaluated promoters P(araBAD), P(rhaBAD) and P(tet), which can be induced with L-arabinose, L-rhamnose or anhydrotetracycline, respectively. EcN harboring promoter constructs with luciferase as reporter gene were administered either orally to healthy mice or intravenously to tumor bearing animals. Subsequent to bacterial colonization of tissues, inducer substances were administered via the oral or systemic route. By use of in vivo bioluminescence imaging, the time course of reporter gene expression was analyzed. Each promoter displayed a specific in vivo induction profile depending on the niche of bacterial residence and the route of inducer administration. Importantly, we also observed colonization of gall bladders of mice when EcN was administered systemically at high doses. Bacteria in this anatomical compartment remained accessible to remote control of bacterial gene expression.
益生菌大肠杆菌 Nissle 1917（EcN）可以作为一种有前途的载体，将异源治疗分子递送到人体用于治疗多种疾病。为了增加这种载体系统的多功能性，细菌应该配备表达模块，可以以时间和定量的方式进行有目的的调控。这种方法被称为细菌载体的体内远程控制（IVRC）。在这里，我们评估了可以分别用 L-阿拉伯糖、L-鼠李糖或脱羟四环素诱导的启动子 P(araBAD)、P(rhaBAD)和 P(tet)。携带荧光素酶报告基因的 EcN 构建体被口服给予健康小鼠或静脉内给予荷瘤动物。在细菌定殖组织后，通过口服或系统途径给予诱导剂物质。通过体内生物发光成像分析报告基因表达的时间过程。每个启动子根据细菌定植部位和诱导剂给药途径显示出特定的体内诱导谱。重要的是，当 EcN 以高剂量系统给予时，我们还观察到小鼠胆囊的定植。该解剖部位的细菌仍然可以进行细菌基因表达的远程控制。
