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

Authors

  • Marc L. Lesnick,

    1. Department of Medicine 0640, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
    Search for more papers by this author
  • Neil E. Reiner,

    1. Department of Medicine, Division of Infectious Diseases, and the Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
    Search for more papers by this author
  • Joshua Fierer,

    1. Department of Medicine 0640, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
    2. Department of Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
    3. Department of Veterans Affairs Medical Center,
      San Diego, CA 92161, USA.
    Search for more papers by this author
  • Donald G. Guiney

    Corresponding author
    1. Department of Medicine 0640, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
    • *For correspondence. E-mail dguiney@ucsd.edu; Tel. (+1) 858 534 6030; Fax (+1) 858 534 6020.

    Search for more papers by this author

Abstract

ADP-ribosylating enzymes, such as cholera and diphtheria toxins, are key virulence factors for a variety of extracellular bacterial pathogens but have not been implicated previously during intracellular pathogenesis. Salmonella strains are capable of invading epithelial cells and localizing in macrophages 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 spvB encodes an ADP-ribosylating enzyme that uses actin as a substrate and depolymerizes actin filaments when expressed in CHO cells. Furthermore, site-directed mutagenesis demonstrates that the ADP-ribosylating activity of SpvB is essential for Salmonella virulence in mice. As spvB is expressed by Salmonella strains after invasion of epithelial cells or phagocytosis by macrophages, these results suggest that SpvB functions as an intracellular ADP-ribosylating toxin critical for the pathogenesis of Salmonella infections.

Ancillary