Prof. Dr. Klaus Aktories
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 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).
His research interest is focused on cell signaling and its manipulation by bacterial protein toxins. His laboratory studies the interaction of toxins with target cells and the host receptors involved in toxin up-take and intracellular traffic. His group discovered the molecular mechanism of numerous bacterial toxins acting by ADP-ribosylation, glycosylation and deamidation of eukaryotic target proteins. Scientific aims are elucidation of the mode of actions of bacterial protein toxins as a prerequisite for development of anti-infection strategies and to use highly specific and potent toxins as pharmacological tools in cell biology and therapy.
- Schwan C, Kruppke AS, Nolke T, Schumacher L, Koch-Nolte F, Kudryashev M, Stahlberg H, and Aktories K Clostridium difficile toxin CDT hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence. Proc Natl Acad Sci U S A 111, 2313-2318 (2014)
- Gatsogiannis C, Lang AE, Meusch D, Pfaumann V, Hofnagel O, Benz R, Aktories K, and Raunser S A syringe-like injection mechanism in Photorhabdus luminescens toxins. Nature 495, 520-523 (2013)
- Jank T, Bogdanovic X, Wirth C, Haaf E, Spoerner M, Bohmer KE, Steinemann M, Orth JH, Kalbitzer HR, Warscheid B, Hunte C, Aktories K. A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins. Nat Struct Mol Biol 20, 1273-1280 (2013)
- Papatheodorou P, Carette JE, Bell GW, Schwan C, Guttenberg G, Brummelkamp TR, and Aktories K. Lipolysis-stimulated lipoprotein receptor (LSR) is the host receptor for the binary toxin Clostridium difficile transferase (CDT). Proc Natl Acad Sci USA 108, 16422-16427 (2011).
- Lang AE, Schmidt G, Schlosser A, Hey TD, Larrinua IM, Sheets JJ, Mannherz H-G, and Aktories K. Photorhabdus luminescens toxins ADP-ribosylate actin and RhoA to force actin clustering. Science 327, 1139-1142 (2010).
Role of membrane dynamics, intracellular trafficking and autophagosomal processes in cytotoxicity of Rho-modifying bacterial protein toxins
Rho proteins are essential GTP-binding proteins, which act as molecular switches in numerous cellular functions. Clostridium difficile toxins A (TcdA) and B (TcdB) and Escherichia coli Cytotoxic Necrotizing Factor (CNF) 1, which are crucial pathogenicity factors in colitis and urinary tract infections, inactivate and activate Rho proteins by glucosylation and deamidation, respectively. This alters Rho-dependent signaling and results in disease. To elucidate the precise mode of action of the toxins and to develop new therapeutic strategies, we aim to analyze the cellular toxin trafficking and clarify the role of autophagy in cytotoxicity. Using immunofluorescence with specific marker proteins, we will investigate membrane dynamics, vesicle transport of toxins and toxin translocation into the cytosol. shRNA knock downs and dominant negative and positive mutants of Rho proteins will be employed to delineate the specific functions of Rho, Rac and Cdc42 isoforms in autophagy and to elucidate the functional consequences of their modification by toxins.