Figure 3.

Cytolethal Distending Toxin pathway from the bacteria to the host nucleus. In E. coli, E. albertii, S. dysenteriae, S. boydii, and P. alcalifaciens, the CDT operon contains 3 genes that synthetize the 3 subunits CdtA (red), CdtB (green), and CdtC (blue) that are translocated and assembled in the periplasm. Following secretion, CDT binds to a nonidentified receptor on the host eukaryotic cell. Following internalization, CdtB is retrotransported through the Golgi apparatus. Through an ERAD-like pathway, CdtB reaches the nucleus and host DNA. Alternatively, CDT is trapped in OMVs that can deliver the toxin into the host cell by fusion with the plasma membrane or through binding to a receptor. S. Typhi is an intracellular pathogen remaining in the cytosol in the Salmonella-containing vacuole (SCV). CdtB is encoded on a CdtB islet (or SPI-11) together with pltA (fuchsia) and pltB (orange). These gene products form the typhoid toxin that contains 2 “active” subunits (CdtB and PltA) and a pentameric “binding” subunit (PltB). The toxin might be entrapped in OMVs and secreted through vacuoles that exit from the SCV and intoxicates cells through autocrine and paracrine pathways. ERAD, endoplasmic reticulum-associated degradation; OMV, outer membrane vesicle; SPI, Salmonella pathogenicity island; plt, pertussis-like toxin).