2.50
Hdl Handle:
http://hdl.handle.net/10033/23852
Title:
In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit.
Authors:
Royo, José Luis; Becker, Pablo Daniel; Camacho, Eva María; Cebolla, Angel; Link, Claudia; Santero, Eduardo; Guzmán, Carlos Alberto
Abstract:
Systems allowing tightly regulated expression of prokaryotic genes in vivo are important for performing functional studies of bacterial genes in host-pathogen interactions and establishing bacteria-based therapies. We integrated a regulatory control circuit activated by acetyl salicylic acid (ASA) in attenuated Salmonella enterica that carries an expression module with a gene of interest under control of the XylS2-dependent Pm promoter. This resulted in 20-150-fold induction ex vivo. The regulatory circuit was also efficiently induced by ASA when the bacteria resided in eukaryotic cells, both in vitro and in vivo. To validate the circuit, we administered Salmonella spp., carrying an expression module encoding the 5-fluorocytosine-converting enzyme cytosine deaminase in the bacterial chromosome or in a plasmid, to mice with tumors. Induction with ASA before 5-fluorocytosine administration resulted in a significant reduction of tumor growth. These results demonstrate the usefulness of the regulatory control circuit to selectively switch on gene expression during bacterial infection.
Affiliation:
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas, Carretera, Utrera, Km 1, E-41013 Sevilla, Spain.
Citation:
In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit. 2007, 4 (11):937-42 Nat. Methods
Journal:
Nature methods
Issue Date:
Nov-2007
URI:
http://hdl.handle.net/10033/23852
DOI:
10.1038/nmeth1107
PubMed ID:
17922017
Type:
Article
Language:
en
ISSN:
1548-7091
Appears in Collections:
publications of the research group vaccinology and applied microbiology (VAC)

Full metadata record

DC FieldValue Language
dc.contributor.authorRoyo, José Luis-
dc.contributor.authorBecker, Pablo Daniel-
dc.contributor.authorCamacho, Eva María-
dc.contributor.authorCebolla, Angel-
dc.contributor.authorLink, Claudia-
dc.contributor.authorSantero, Eduardo-
dc.contributor.authorGuzmán, Carlos Alberto-
dc.date.accessioned2008-04-21T08:57:33Z-
dc.date.available2008-04-21T08:57:33Z-
dc.date.issued2007-11-
dc.identifier.citationIn vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit. 2007, 4 (11):937-42 Nat. Methodsen
dc.identifier.issn1548-7091-
dc.identifier.pmid17922017-
dc.identifier.doi10.1038/nmeth1107-
dc.identifier.urihttp://hdl.handle.net/10033/23852-
dc.description.abstractSystems allowing tightly regulated expression of prokaryotic genes in vivo are important for performing functional studies of bacterial genes in host-pathogen interactions and establishing bacteria-based therapies. We integrated a regulatory control circuit activated by acetyl salicylic acid (ASA) in attenuated Salmonella enterica that carries an expression module with a gene of interest under control of the XylS2-dependent Pm promoter. This resulted in 20-150-fold induction ex vivo. The regulatory circuit was also efficiently induced by ASA when the bacteria resided in eukaryotic cells, both in vitro and in vivo. To validate the circuit, we administered Salmonella spp., carrying an expression module encoding the 5-fluorocytosine-converting enzyme cytosine deaminase in the bacterial chromosome or in a plasmid, to mice with tumors. Induction with ASA before 5-fluorocytosine administration resulted in a significant reduction of tumor growth. These results demonstrate the usefulness of the regulatory control circuit to selectively switch on gene expression during bacterial infection.en
dc.language.isoenen
dc.subject.mesh3-Phosphoshikimate 1-Carboxyvinyltransferaseen
dc.subject.meshAnimalsen
dc.subject.meshAspirinen
dc.subject.meshBacterial Proteinsen
dc.subject.meshCell Line, Tumoren
dc.subject.meshFlucytosineen
dc.subject.meshFluorouracilen
dc.subject.meshGene Expressionen
dc.subject.meshGene Expression Regulation, Bacterialen
dc.subject.meshGenetic Engineeringen
dc.subject.meshGreen Fluorescent Proteinsen
dc.subject.meshHela Cellsen
dc.subject.meshHumansen
dc.subject.meshLac Operonen
dc.subject.meshMacrophagesen
dc.subject.meshMiceen
dc.subject.meshNeoplasmsen
dc.subject.meshOperonen
dc.subject.meshPromoter Regions (Genetics)en
dc.subject.meshSalmonella Infectionsen
dc.subject.meshSalmonella entericaen
dc.subject.meshSodium Salicylateen
dc.subject.meshSpleenen
dc.subject.meshTranscription Factorsen
dc.subject.meshbeta-Galactosidaseen
dc.titleIn vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit.en
dc.typeArticleen
dc.contributor.departmentCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas, Carretera, Utrera, Km 1, E-41013 Sevilla, Spain.en
dc.identifier.journalNature methodsen

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