title: Novel tools to analyze the function of Salmonella effectors show that SvpB ectopic expression induces cell cycle arrest in tumor cells.
abstract: In order to further characterize its role in pathogenesis and to establish whether its overproduction can lead to eukaryotic tumor cell death, Salmonella strains able to express its virulence factor SpvB (an ADP-ribosyl transferase enzyme) in a salicylate-inducible way have been constructed and analyzed in different eukaryotic tumor cell lines. To do so, the bacterial strains bearing the expression system have been constructed in a ∆purD background, which allows control of bacterial proliferation inside the eukaryotic cell. In the absence of bacterial proliferation, salicylate-induced SpvB production resulted in activation of caspases 3 and 7 and apoptotic cell death. The results clearly indicated that controlled SpvB production leads to F-actin depolimerization and either G1/S or G2/M phase arrest in all cell lines tested, thus shedding light on the function of SpvB in Salmonella pathogenesis. In the first place, the combined control of protein production by salicylate regulated vectors and bacterial growth by adenine concentration offers the possibility to study the role of Salmonella effectors during eukaryotic cells infection. In the second place, the salicylate-controlled expression of SpvB by the bacterium provides a way to evaluate the potential of other homologous or heterologous proteins as antitumor agents, and, eventually to construct novel potential tools for cancer therapy, given that Salmonella preferentially proliferates in tumors.
authors.affiliation: Centro Andaluz de Biología del Desarrollo/ CSIC/ Universidad Pablo de Olavide/ Junta de Andalucía. Departamento de Biología Molecular e Ingeniería Bioquímica, Seville, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mesa-Pereira
authors.forename: Carlos
authors.initials: C
authors.lastname: Medina
authors.forename: Eva María
authors.initials: EM
authors.lastname: Camacho
authors.forename: Amando
authors.initials: A
authors.lastname: Flores
authors.forename: Eduardo
authors.initials: E
authors.lastname: Santero
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics*; D000199:Actins / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics*; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D012475:Salmonella / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000199:Actins; D037521:Virulence Factors; D036002:ADP Ribose Transferases; D053148:Caspase 3