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AbstractSystemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.
CitationComposing a Tumor Specific Bacterial Promoter. 2016, 11 (5):e0155338 PLoS ONE
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
- Identification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic.
- Authors: Leschner S, Deyneko IV, Lienenklaus S, Wolf K, Bloecker H, Bumann D, Loessner H, Weiss S
- Issue date: 2012 Apr
- Expression of in vivo-inducible Salmonella enterica promoters during infection of Caenorhabditis elegans.
- Authors: Van Gerven N, Derous V, Hernalsteens JP
- Issue date: 2008 Jan
- In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit.
- Authors: Royo JL, Becker PD, Camacho EM, Cebolla A, Link C, Santero E, Guzmán CA
- Issue date: 2007 Nov
- Salmonella promoters preferentially activated inside tumors.
- Authors: Arrach N, Zhao M, Porwollik S, Hoffman RM, McClelland M
- Issue date: 2008 Jun 15
- Development of a flexible and potent hypoxia-inducible promoter for tumor-targeted gene expression in attenuated Salmonella.
- Authors: Mengesha A, Dubois L, Lambin P, Landuyt W, Chiu RK, Wouters BG, Theys J
- Issue date: 2006 Sep