Translocation of a Vibrio cholerae type VI secretion effector requires bacterial endocytosis by host cells

Cell Host Microbe. 2009 Mar 19;5(3):234-43. doi: 10.1016/j.chom.2009.02.005.


The type VI secretion system (T6SS) is a virulence mechanism common to several Gram-negative pathogens. In Vibrio cholerae, VgrG-1 is required for T6SS-dependent secretion. VgrG-1 is also secreted by T6SS and displays a C-terminal actin crosslinking domain (ACD). Using a heterologous reporter enzyme in place of the ACD, we show that the effector and secretion functions of VgrG-1 are genetically dissociable with the ACD being dispensable for secretion but required for T6SS-dependent phenotypes. Furthermore, internalization of bacteria is required for ACD translocation into phagocytic target cells. Inhibiting bacterial uptake abolishes actin crosslinking, while improving intracellular survival enhances it. Otherwise resistant nonphagocytic cells become susceptible to T6SS-mediated actin crosslinking when engineered to take up bacteria. Our results support a model for translocation of VgrG C-terminal effector domains into target cell cytosol by a process that requires trafficking of bacterial cells into an endocytic compartment where translocation is triggered by an unknown signal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Endocytosis
  • Gene Deletion
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Models, Biological
  • Phagocytes / immunology*
  • Phagocytes / microbiology*
  • Protein Structure, Tertiary
  • Vibrio cholerae / metabolism*
  • Vibrio cholerae / pathogenicity*
  • Virulence Factors / genetics
  • Virulence Factors / toxicity*


  • Actins
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Virulence Factors