Cytotoxins of Vibrio vulnificus: Functions and roles in pathogenesis

Vibrio vulnificus, a marine Gram-negative bacterium, may cause systemic infections in humans and eels. In humans, particularly those with chronic liver disorders, this organism produces severe soft tissue damage via infecting a wound and fulminant sepsis with a high mortality rate in those who ingest contaminated shellfish. The ability of V. vulnificus to invade the bloodstream from an intact gastrointestinal tract and cause hemorrhagic necrosis of soft tissue, the most prominent features of its infectious disease, has been the focus of studies on the pathogenesis mechanism. This organism is cytotoxic to a variety of host cells, and this property may be associated with its invasiveness and tissue damaging ability. Two cytotoxins, VvhA and MARTXVv, have been identified. The former exhibits pathological effects resembling those observed in patients, however, it plays only minor roles in cytotoxicity to cocultured host cells and virulence in a mouse model. MARTXVv has a predicted molecular weight of 556 kDa, and neither the full-length protein nor processed peptides have been purified. This has hampered research on its functions and mechanism of cytotoxicity. Nevertheless, by characterizing the MARTXVv-deficient mutants, this cytotoxin has been demonstrated to be required for survival of V. vulnificus at the primary infection site and internal organs as well by preventing the organism from engulfment by the phagocytes. The identification of the functional domains in MARTXVv should facilitate future studies to reveal how this toxin blocks phagocytosis and causes cell lysis.