Bacterial Protein Toxins as Tools in Cell Biology and Pharmacology

Abstract

At least four properties of bacterial protein toxins make them suitable as cell biological and pharmacological tools. First, the toxins enter cells without damaging the cell integrity. Second, the toxins possess high specificity. A high cell specificity is most often based on a toxin-specific membrane-binding domain and on specific receptors present on the surface of eukaryotic target cells. Actin, another important eukaryotic substrate for ADP-ribosylation by bacterial toxins, is not a GTP-binding protein but an ATP-binding protein. Because all these nucleotide-binding proteins are functionally important cellular proteins, the toxins, which allow their selective covalent modification, are widely used as tools. The actin cytoskeleton is the target of various bacterial toxins that affect the microfilament protein either directly by ADP-ribosylation or indirectly by modifying the regulatory mechanisms involved in the organization of the actin cytoskeleton. Actin, which is one of the most abundant proteins in eukaryotic cells, is the major component of the microfilament system. The toxin effect should occur with some delay of at least 15 to 30 min. This time is necessary for the translocation of the toxin. Moreover, it should be tested whether actin is in fact ADP-ribosylated by the toxin. Hydrolysis of bound GTP terminates the active state of the GTPases. It has been shown that especially Rho subfamily GTPases are targets for bacterial protein toxins. Recently, the genes for toxins were introduced into some crop plants in an effort to protect them from insect attack.