In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit.
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Authors
Royo, José LuisBecker, Pablo Daniel
Camacho, Eva María
Cebolla, Angel
Link, Claudia
Santero, Eduardo
Guzmán, Carlos Alberto
Issue Date
2007-11
Metadata
Show full item recordAbstract
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. MethodsAffiliation
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas, Carretera, Utrera, Km 1, E-41013 Sevilla, Spain.Journal
Nature methodsPubMed ID
17922017Type
ArticleLanguage
enISSN
1548-7091ae974a485f413a2113503eed53cd6c53
10.1038/nmeth1107
Scopus Count
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