Targeting toxins!: Drug delivery with poisons

Many organisms produce potently toxic proteins that act on other cells, sometimes with lethal effects. In this way, such proteins help to increase the chance of survival or proliferation of the producing organism. Moreover, a lot of toxins have an exquisitely specific action. For example, proteins studied in the Warwick toxin laboratory -- ricin, a toxin from the castor oil seed (Figure 1), and its relatives from the pathogenic Escherichia coli 0157 and the dysentery-causing bacterium (Shigella dysenteriae), have evolved to selectively target ribosomes within the cells of susceptible organisms, thereby enabling a fatal disruption of protein synthesis. What is very striking is the clever way these particular toxins exploit intracellular transport pathways to travel from the cell surface to their substrates in the cytosol. Once delivered there, each toxin molecule can disable approximately 2000 polysomes per minute, enough to eventually kill the cell. Research is now aimed at elucidating the molecular details of the cellular uptake of ricin and the Shiga family of toxins, and of exploiting their unusual trafficking properties for biotechnological purposes.