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    Keywords: CANCER ; EXPRESSION ; tumor ; Germany ; IN-VIVO ; THERAPY ; VIVO ; SYSTEMS ; GENE ; GENE-EXPRESSION ; MOLECULES ; TISSUE ; MICE ; INDUCTION ; gene expression ; ESCHERICHIA-COLI ; VECTOR ; PROMOTER ; NETHERLANDS ; BIOLUMINESCENCE ; ENGINEERED BACTERIA ; Gall bladder ; In vivo imaging ; Inducible promoter ; Organ colonization ; Tumor targeted bacteria
    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 ill 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.
    Type of Publication: Journal article published
    PubMed ID: 19665575
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