Struggling to get a universal meningococcal vaccine and novel uses for bacterial toxins in cancer treatment

Abstract

In the Early View section of Microbial Biotechnology online Engedal and colleagues (2010) provide an extensive review of the Shiga toxin and its use in targeted cancer therapy and imaging. Shiga toxins are produced by Shigella dysenteriae and some strains of Escherichia coli. The toxins are composed of two non‐covalently linked, modular parts: the A moiety (StxA) which contains the enzymatically active A1 fragment, and the non‐toxic, pentameric binding moiety (StxB). A unique property of Stx is that it binds specifically to the glycosphingolipid globotriaosylceramide (Gb3) located on the surface of target cells and is then internalized by endocytosis. Consequently, in toxin‐sensitive cells, the Stx/Gb3 complex is transported to the endoplasmic reticulum through the Golgi apparatus, the StxA is then translocated to the cytosol, where it irreversibly inhibits protein synthesis by means of modification of ribosomal 28S RNA. Interestingly, Gb3 shows a relatively restricted expression in normal human tissues, and has been reported to be highly expressed in many types of cancers.