title: Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.
abstract: 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.
authors: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Inhoffenstrasse 7, 38124 Braunschweig, Germany. loeho@pei.de
authors: Holger
authors: H
authors: Loessner
authors: Sara
authors: S
authors: Leschner
authors: Anne
authors: A
authors: Endmann
authors: Kathrin
authors: K
authors: Westphal
authors: Kathrin
authors: K
authors: Wolf
authors: Katja
authors: K
authors: Kochruebe
authors: Tewfik
authors: T
authors: Miloud
authors: Josef
authors: J
authors: Altenbuchner
authors: Siegfried
authors: S
authors: Weiss
mesh_terms: D000818:Animals; D001089:Arabinose / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D005260:Female; D005704:Gallbladder / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D007422:Intestines / Q000382:microbiology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000382:microbiology*; D019936:Probiotics; D011401:Promoter Regions, Genetic; D012210:Rhamnose / Q000008:administration & dosage / Q000494:pharmacology; D012878:Skin Neoplasms / Q000382:microbiology; D013754:Tetracyclines / Q000008:administration & dosage / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D013754:Tetracyclines; C016229:4-epianhydrotetracycline; D001089:Arabinose; D008156:Luciferases; D012210:Rhamnose