MARTX toxins are the largest secreted bacterial protein toxins. Toxins in this family share highly conserved “repeat regions” at the N- and C-termini. which are required for toxin secretion from the bacterium and to form a pore in the eukaryotic cell membrane. A MARTX toxin is essential for virulence of the Gram-negative pathogen Vibrio vulnificus. This bacterium causes severe wound infections predominantly from swimming and fishing that can rapidly progress to sepsis and necrotizing fasciitis, resulting in death. V. vulnificus food-borne infections are closely linked with consumption of seafood and predominantly arise in persons with liver cirrhosis, diabetes, and other underlying conditions. During intestinal infection with V. vulnificus, the MARTX toxin is essential to act against intestinal epithelial cells to break the epithelial barrier for transmission of the bacterium to the bloodstream only hours after infection. These toxin have both pore-forming and multiple catalytic activities. Data will be presented showing that it is the effector domain activity, and not the pore forming necrotic activity of the toxin, that is essential for intestinal barrier breach. Further, the breach occurs well before the onset of overt intestinal damage.