Vibrio vulnificus MARTX toxin effector domains differentially remodel the transcriptional response of intestinal epithelial cells

Vibrio vulnificus is an foodborne pathogen that can cause gastroenteritis and septicemia in humans. V. vulnificus secretes a multifunctional autoprocessing repeats-in-toxin (MARTX) toxin as an essential virulence factor to cause disease. MARTX toxins are pore-forming toxins that translocate multiple functionally independent effector domains into a target cell. MARTX toxins of V. vulnificus can contain anywhere from 3 to 5 of the 10 identified effector domains and strains with different effector repertories having varying virulence potential. The goal of this study was to compare how different effector combinations from an F-type MARTX toxin differentially remodel the transcriptional response of human intestinal epithelial cells (IECs). F-type MARTX toxins contain five effector domains – the actin crosslinking domain (ACD), two copies the makes caterpillar floppy-like domain (MCF), and alpha-beta hydrolase (ABH) domain, and the Ras/Rap1 specific endopeptidase (RRSP). Cultured human IECs were treated with V. vulnificus or strains modified to secrete a toxin with only ACD, ACD with MCF-ABH, ACD with RRSP, or no active effectors. We demonstrate that when no active effectors are present, the bacterium induces minimal changes in the transcriptional profile of IECs. However, the strains containing different effector combinations each uniquely remodeled the transcriptional profile of IECs. These data provide insight into how V. vulnificus strains with varying effector combinations can differentially regulate the host cell response to cause disease. T84 human colonic epithelial cells were inoculated with 98-783-DP-A1 Vibrio vulnificus containing the wild type F-type MARTX toxin or strains generated to contain MARTX toxins with varying effector combinations. mRNA from inoculated T84 cells was extracted for RNA-sequencing. Each processed file is in .xlsx file type and contain official gene symbol, fold changes compared to PBS treated controls, and p-vaules indicating statistically significant or non-significant changes in gene expression compared to PBS treated controls.