RNA-sequencing analysis examining how the Vibrio cholerae MARTX toxin and its inidividual effector domains modulate the transcriptome of human intestinal epithelial cells.

MARTX toxins are large single polypeptide bacterial toxins that translocate multiple cytotoxic and functionally independent effector domains into the cytosol of a target eukaryotic cell. Pandemic Vibrio cholerae El Tor O1 strains secrete a MARTX toxin with three effector domains — the actin crosslinking domain (ACD), the Rho inactivation domain (RID), and the alpha/beta-hydrolase domain (ABH) — to regulate innate immunity and enhance colonization. The goal of this study was to compare changes in the transcriptome of human intestinal epithelial cells (IECs) treated with V. cholerae modified to secret a toxin with only one effector domain to the transcriptome of cells treated with V. cholerae secreting the wild type MARTX toxin that delivers all three effector domains simultaneously. We demonstrate that when all three effectors are delivered there is no change in transcriptional response of IECs compared to untreated cells. However, when only ACD is delivered, transcriptional profiling revealed a significant proinflammatory response is activated. These data suggests that V. cholerae may utilize co-delivery of RID and/or ABH to silence the intestinal immune response to ACD activity. These data provide insight into how the V. cholerae MARTX toxin effector domains function together to alter the innate immune response of IECs during bacterial infection. Overall design: mRNA expression profile of T84 human colonic epithielial cells inoculated with N16961?hlyA?hapA V. cholerae containing the wild type MARTX toxin or strains generated to contain MARTX toxins with only a single effector domain. Each processed file is in .xlsx file type and contain offical gene symbol and description for each gene, read counts for each replicate, fold changes compared to PBS treated controls, and p-values indicating statistically significant or non-significant changes in gene expression compared to PBS treated controls.