MARTX toxin effector domains modulate virulence of foodborne Vibrio vulnficus

As reported by the USDA, infections by Vibrio vulnificus bacteria are the most economically burdensome foodborne illness per case in the United States. V. vulnificus-­‐associated fatality rates from food borne illness exceed 50 percent. Yet, the bacteria’s major virulence factor and its relationship to foodborne infection remain poorly understood. As infection incidence climbs in conjunction with rising sea surface temperature due to climate change, studies elucidating pathogenic mechanisms of V. vulnificus are increasingly critical to addressing the 2016 USDA AFRI Food Safety Challenge Area and Foundational Area on Food Safety, Nutrition, and Health. The proposed study investigates the MARTX toxin, the dominant virulence factor in V. vulnificus intestinal infection. We have identified the region of the toxin – the effector domain repertoire – that promotes dissemination of bacteria from intestine to bloodstream. Because bacterial dissemination is associated with poor clinical outcomes, our first objective investigates mechanisms by which MARTX effector domains collectively promote dissemination and lethal disease. Our second objective explores the virulence potential of strains expressing different combinations of effector domains within the MARTX toxin effector domain repertoire; this question is key to understanding potency of the many existing MARTX toxin variants. Objectives will be addressed using novel bacterial strains in a combination of in vitro cellular assays and in vivo animal models. Results of this study will inform new strategies for the generation of vaccines, therapeutics, and diagnostics to combat lethal foodborne V. vulnificus infection.