Abstract
The cytoskeleton plays crucial roles in host-pathogen interaction. It is essential for epithelial barrier functions, phagocytosis and regulation of immune cell signaling, including cytokine release or production of reactive oxygen species. The cytoskeleton (especially the actin cytoskeleton) is a preferred target of bacterial toxins and effectors. Many bacterial toxins/effectors manipulate the cytoskeleton by targeting small GTPases of the Rho family. The toxins cause ADP-ribosylation, glycosylation, adenylylation, deamidation and proteolysis of Rho proteins, resulting in activation or inactivation of Rho GTPases. Other toxins/effectors hijack functions of eukaryotic Rho regulators. Again another group of bacterial protein toxins directly modifies actin by ADP-ribosylation, thereby causing inhibition or stimulation of actin polymerization, depending on the site of modification. The presentation focuses on modification of actin and of Rho proteins induced by bacterial protein toxins, which are produced by Clostridia and Photorhabdus species.
Biography
Klaus Aktories studied Pharmacy and Medicine at the University of Frankfurt, where he received the degree Dr. med. (1977). He was Research Associate in Pharmacology at the University of Heidelberg (laboratory of Günter Schulz) from 1978-1984, received 1981 the degree Dr. rer. nat. (Ph.D.) and 1983 the Habilitation for Pharmacology and Toxicology. He was Associate Professor in Pharmacology at the University of Gießen (1985-1989) and Essen (1989-1991). From 1991-1994 he was Full Professor in Pharmacology at the University of the Saarland. Since 1995 he is Full Professor and Chair (Department 1) in Pharmacology and Toxicology at the University of Freiburg, Germany. He is member of the German National Academy of Sciences – Leopoldina (2003), fellow of the American Academy of Microbiology (2008) and Member of EMBO (2008).
Research interest
His scientific career started in pharmacology with research on signal transduction of G protein-coupled receptors and their manipulation by bacterial protein toxins (Ph.D. and post-doc). Since that time his main interest is focused on the analysis of molecular mechanisms of bacterial protein toxins and their structure-function relationships. His laboratory identified actin as the specific target of several clostridial ADP-ribosylating toxins and discovered the Rho-modifying toxin C3. His group discovered the molecular mechanism of the cytotoxic effects of C. difficile toxins A and B as glucosylation of Rho proteins and characterized several other clostridial glycosyltransferases including C. sordellii toxin, C. novyi α-toxin and C. perfringens TpeL toxin. His group identified the molecular mechanisms of Legionella pneumophila glucosyltransferase Lgt as modification of elongation factor 1A (collaboration with Yury Belyi, Moscow) and elucidated the molecular mechanisms of deamidating toxin from E. coli (e.g., CNFs), Pasteurella multocida (e.g., PMT) and Photorhabdus species. Recently, his laboratory discovered the tyrosine GlcNAcylation of Rho proteins by Photorhabdus asymbiotica toxin PaTox. Identification of host cell receptors (e.g., LSR and LRP1) of toxins is another recent focus of his laboratory.