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.