title: Identification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic.
abstract: Conventional cancer therapies are often limited in effectiveness and exhibit strong side effects. Therefore, alternative therapeutic strategies are demanded. The employment of tumor-colonizing bacteria that exert anticancer effects is such a novel approach that attracts increasing attention. For instance, Salmonella enterica serovar Typhimurium has been used in many animal tumor models as well as in first clinical studies. These bacteria exhibit inherent tumoricidal effects. In addition, they can be used to deliver therapeutic agents. However, bacterial expression has to be restricted to the tumor to prevent toxic substances from harming healthy tissue. Therefore, we screened an S. Typhimurium promoter-trap library to identify promoters that exclusively drive gene expression in the cancerous tissue. Twelve elements could be detected that show reporter gene expression in tumors but not in spleen and liver. In addition, a DNA motif was identified that appears to be necessary for tumor specificity. Now, such tumor-specific promoters can be used to safely express therapeutic proteins by tumor-colonizing S. Typhimurium directly in the neoplasia.
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany. sara.leschner@helmholtz-hzi.de
authors.forename: Sara
authors.initials: S
authors.lastname: Leschner
authors.forename: Igor V
authors.initials: IV
authors.lastname: Deyneko
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wolf
authors.forename: Helmut
authors.initials: H
authors.lastname: Bloecker
authors.forename: Dirk
authors.initials: D
authors.lastname: Bumann
authors.forename: Holger
authors.initials: H
authors.lastname: Loessner
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000382:microbiology*; D059372:Nucleotide Motifs; D011401:Promoter Regions, Genetic; D012486:Salmonella typhimurium / Q000235:genetics*; D017422:Sequence Analysis, DNA