Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.
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Authors
Loessner, HolgerLeschner, Sara
Endmann, Anne
Westphal, Kathrin
Wolf, Kathrin
Kochruebe, Katja
Miloud, Tewfik
Altenbuchner, Josef
Weiss, Siegfried
Issue Date
2009-12
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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.Citation
Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice. 2009, 11 (14-15):1097-105 Microbes Infect.Affiliation
Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Inhoffenstrasse 7, 38124 Braunschweig, Germany. loeho@pei.dePubMed ID
19665575Type
ArticleLanguage
enISSN
1769-714Xae974a485f413a2113503eed53cd6c53
10.1016/j.micinf.2009.08.002
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