RRSP and RID Effector Domains Dominate Virulence Impact of Vibrio vulnificus MARTX Toxin.

Background: The bacterial pathogen Vibrio vulnificus causes severe septic foodborne infections. The multifunctional autoprocessing repeats-in-toxins (MARTX) toxin is an important secreted virulence factor. The effector domain region is essential for lethal intestinal infection in mice, but the contribution of each of the five effector domains to infection has not been investigated.

Methods: V. vulnificus mutants with varying effector domain content were inoculated intragastrically to mice and time-to-death was monitored to establish the contribution of each effector domain to overall virulence. Each strain was also tested for bacterial dissemination from the intestine to internal organs and for inhibition of phagocytosis.

Results: The effector domain region was required for V. vulnificus to inhibit phagocytosis by J774 macrophages, but no single effector domain was required. No single MARTX effector domain was necessary for bacterial dissemination. Nonetheless, overall survival of infected mice did differ dependent upon the infecting V. vulnificus strain. Removal of rid or rrsp significantly reduced V. vulnificus virulence potential, while deletion of duf1 or abh accelerated time to death.

Conclusion: RID and RRSP each exert greater effects on virulence compared to other MARTX domains suggesting that modulation of Rho/Ras family GTPases is a critical function of the toxin during intestinal infection.