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In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit.

Royo, José Luis
; 
Becker, Pablo Daniel
; 
Camacho, Eva María
; 
Cebolla, Angel
; 
Link, Claudia
; 
Santero, Eduardo
; 
Guzmán, Carlos Alberto
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2007-11
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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.
Citation
In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit. 2007, 4 (11):937-42 Nat. Methods
Affiliation
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas, Carretera, Utrera, Km 1, E-41013 Sevilla, Spain.
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Journal
Nature methods
URI
http://hdl.handle.net/10033/23852
DOI
10.1038/nmeth1107
PubMed ID
17922017
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Article
Language
en
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ISSN
1548-7091
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publications of the research group vaccinology and applied microbiology (VAC)