Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.

2.50
HDL Handle:
http://hdl.handle.net/10033/96597
Title:
Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.
Authors:
Loessner, Holger; Leschner, Sara; Endmann, Anne; Westphal, Kathrin; Wolf, Kathrin; Kochruebe, Katja; Miloud, Tewfik; Altenbuchner, Josef; Weiss, Siegfried
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.
Affiliation:
Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Inhoffenstrasse 7, 38124 Braunschweig, Germany. loeho@pei.de
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.
Journal:
Microbes and infection / Institut Pasteur
Issue Date:
Dec-2009
URI:
http://hdl.handle.net/10033/96597
DOI:
10.1016/j.micinf.2009.08.002
PubMed ID:
19665575
Type:
Article
Language:
en
ISSN:
1769-714X
Appears in Collections:
Publications of RG Mucosal Immunity (MI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorLoessner, Holgeren
dc.contributor.authorLeschner, Saraen
dc.contributor.authorEndmann, Anneen
dc.contributor.authorWestphal, Kathrinen
dc.contributor.authorWolf, Kathrinen
dc.contributor.authorKochruebe, Katjaen
dc.contributor.authorMiloud, Tewfiken
dc.contributor.authorAltenbuchner, Josefen
dc.contributor.authorWeiss, Siegfrieden
dc.date.accessioned2010-04-15T12:06:20Z-
dc.date.available2010-04-15T12:06:20Z-
dc.date.issued2009-12-
dc.identifier.citationDrug-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.en
dc.identifier.issn1769-714X-
dc.identifier.pmid19665575-
dc.identifier.doi10.1016/j.micinf.2009.08.002-
dc.identifier.urihttp://hdl.handle.net/10033/96597-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshArabinoseen
dc.subject.meshCell Line, Tumoren
dc.subject.meshEscherichia colien
dc.subject.meshFemaleen
dc.subject.meshGallbladderen
dc.subject.meshGene Expression Regulation, Bacterialen
dc.subject.meshIntestinesen
dc.subject.meshLuciferasesen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshNeoplasms, Experimentalen
dc.subject.meshProbioticsen
dc.subject.meshPromoter Regions, Geneticen
dc.subject.meshRhamnoseen
dc.subject.meshSkin Neoplasmsen
dc.subject.meshTetracyclinesen
dc.subject.meshTissue Distributionen
dc.titleDrug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.en
dc.typeArticleen
dc.contributor.departmentMolecular Immunology, Helmholtz Centre for Infection Research, HZI, Inhoffenstrasse 7, 38124 Braunschweig, Germany. loeho@pei.deen
dc.identifier.journalMicrobes and infection / Institut Pasteuren

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