Figure 12.

Schematic representation of intracellularly active bacterial toxins inducing cell death. Diphtheria toxin (DT) and Pseudomonas aeruginosa exotoxin A (ExoA) deliver their enzymatic domains (A) via early endosomes (EE) and endoplasmic reticulum (ER) pathways, respectively, into the cytosol and inactivate the elongation factor 2 (EF2) by ADP-ribosylation. Shiga toxin (ST) uses a long entry pathway through ER and hydrolysis ribosomal RNA bonds. Bacillus anthracis lethal toxin delivers the lethal factor (LF) via protective antigen (PA) pores through the endosomal membrane and proteolytically cleaves mitogen-activated protein kinase kinases (MAPKKs). Cytolethal distending toxins (CDT) translocate the enzymatic components CdtB into the nucleus, which has DNase activity. Helicobacter pylori vacuolating toxin (VacA) oligomerizes and is internalized via EEs, which can contact mitochondria and transfer the toxin to this organelle. VacA is also delivered from late endosomes (LE) [224]. VacA permeabilizes the mitochondrial membrane leading to the release of cytochrome c (Cyt-c) and apoptosis.