• Identification of tumor-specific Salmonella Typhimurium promoters and their regulatory logic.

      Leschner, Sara; Deyneko, Igor V; Lienenklaus, Stefan; Wolf, Kathrin; Bloecker, Helmut; Bumann, Dirk; Loessner, Holger; Weiss, Siegfried; Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany. sara.leschner@helmholtz-hzi.de (2012-04)
      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.
    • Influence of infection route and virulence factors on colonization of solid tumors by Salmonella enterica serovar Typhimurium.

      Crull, Katja; Bumann, Dirk; Weiss, Siegfried; Dept. Molecular Immunology, Helmholtz Centre for infection research, Inhoffenstr. 7, D38124 Braunschweig, Germany. (2011-06)
      Administration of facultative anaerobic bacteria such as Salmonella enterica serovar Typhimurium as anticancer treatment holds a great therapeutic potential. Here, we tested different routes of application of S. typhimurium with regard to tumor colonization and therapeutic efficacy. No differences between intravenous and intraperitoneal infection were observed, often leading to a complete tumor clearance. In contrast, after oral application, tumor colonization was inefficient and delayed. No therapeutic effect was observed under such conditions. We also showed that tumor invasion and colonization were independent of functional Salmonella pathogenicity island (SPI) 1 and SPI 2. Furthermore, tumor invasion and colonization did not require bacterial motility or chemotactic responsiveness. The distribution of the bacteria within the tumor was independent of such functions.