The Salmonella spvB virulence gene encodes an enzyme that ADP-ribosylates actin and destabilizes the cytoskeleton of eukaryotic cells

ADP-ribosylating enzymes, such as cholera and diphtheria toxins, are key vi rulence factors for a variety of extracellular bacterial pathogens but have not been implicated previously during intracellular pathogenesis. Salmonel la strains are capable of invading epithelial cells and localizing in macro phages during infection. The spvB virulence gene of Salmonella is required for human macrophage cytotoxicity in vitro and for enhancing intracellular bacterial proliferation during infection. Here, we present evidence that sp vB encodes an ADP-ribosylating enzyme that uses actin as a substrate and de polymerizes actin filaments when expressed in CHO cells. Furthermore, site- directed mutagenesis demonstrates that the ADP-ribosylating activity of Spv B is essential for Salmonella virulence in mice. As spvB is expressed by Sa lmonella strains after invasion of epithelial cells or phagocytosis by macr ophages, these results suggest that SpvB functions as an intracellular ADP- ribosylating toxin critical for the pathogenesis of Salmonella infections.