Research Topics
| H BarthSummaryAffiliation: University of Freiburg Country: Germany Publications
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Publications
Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteinsHolger Barth
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, Otto Krayer Haus, Albertstrasse 25, D 79104 Freiburg, Germany
Microbiol Mol Biol Rev 68:373-402, table of contents. 2004..The information may foster future studies that aid novel vaccine and drug development, as well as a better understanding of a conserved intoxication process utilized by various gram-positive, spore-forming bacteria...
The uptake machinery of clostridial actin ADP-ribosylating toxins--a cell delivery system for fusion proteins and polypeptide drugsHolger Barth
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, Otto Krayer Haus, Albertstrasse 25, 79104 Freiburg Germany
Naunyn Schmiedebergs Arch Pharmacol 366:501-12. 2002..g., Rho-ADP-ribosylating C3 exoenzyme) into cells. The present review describes the biological functions of the toxins, focuses on recent studies on the uptake and delivery mechanism and discusses the usage as a drug delivery system...- Uptake of binary actin ADP-ribosylating toxinsH Barth
Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, Otto Krayer Haus, Albertstrasse 25, 79104, Freiburg, Germany
Rev Physiol Biochem Pharmacol 152:165-82. 2004..The second component of these toxins, the binding/translocation component (B), mediates the transport of the enzyme component into the cytosol... - Cellular uptake of Clostridium difficile toxin B. Translocation of the N-terminal catalytic domain into the cytosol of eukaryotic cellsGunther Pfeifer
, Otto-Krayer-Haus, Albertstrasse 25, D-79104 Freiburg, Germany
J Biol Chem 278:44535-41. 2003..The data indicate that toxin B is proteolytically processed during its cellular uptake process... - Cellular uptake of Clostridium botulinum C2 toxin: membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domainGerd Haug
, , Germany
Biochemistry 42:15284-91. 2003..The data indicate that methotrexate prevented unfolding of the C2I-DHFR fusion toxin, and thereby the translocation of methotrexate-bound C2I-DHFR from endosomes into the cytosol of target cells is inhibited... - Channel formation by the binding component of Clostridium botulinum C2 toxin: glutamate 307 of C2II affects channel properties in vitro and pH-dependent C2I translocation in vivoDagmar Blöcker
Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, Otto Krayer Haus, Albertstrasse 25, D 79104 Freiburg, Germany
Biochemistry 42:5368-77. 2003..Overall, the voltage gating and cation selectivity of the C2II channel do not play an important role in translocation of C2I into the cytosol... - Cellular uptake of the Clostridium perfringens binary iota-toxinD Blocker
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, D 79104 Freiburg, Germany
Infect Immun 69:2980-7. 2001..Iota-toxin led to a significant decrease in resistance when it was applied to the basolateral surface of the cells but not following application to the apical surface, indicating a polarized localization of the iota-toxin receptor... - Hypereosinophilia induced by high-dose intratumoral and peritumoral mistletoe application to a patient with pancreatic carcinomaR Huber
Center for Complementary Medicine, Department of Gastroenterology, University of Freiburg, Germany
J Altern Complement Med 6:305-10. 2000..CONCLUSION: Before high-dose intratumoral and peritumoral treatment with a Viscum album L. extract containing mistletoe, lectin 1 can be associated with hypereosinophilia and strong production of TH1 as TH2 cytokines as well... - Regulation of somatodendritic GABAA receptor channels in rat hippocampal neurons: evidence for a role of the small GTPase Rac1D K Meyer
Department of Pharmacology, Albert Ludwigs University, 79104 Freiburg, Germany
J Neurosci 20:6743-51. 2000..It is suggested that Rac1 participates in the regulation of GABA(A) receptor clustering and/or recycling... - Clostridium botulinum C2 toxin--new insights into the cellular up-take of the actin-ADP-ribosylating toxinKlaus Aktories
Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, Freiburg, Germany
Int J Med Microbiol 293:557-64. 2004..The mini-review describes main properties of C2 toxin and discusses new findings on the involvement of chaperones in the up-take process of the toxin... - The binary Clostridium botulinum C2 toxin as a protein delivery system: identification of the minimal protein region necessary for interaction of toxin componentsHolger Barth
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, Albertstrasse 25, D 79104 Freiburg Germany
J Biol Chem 277:5074-81. 2002..C2I(30-225)-C3 did not induce cytotoxic effects on cells when applied together with C2IIa, indicating that amino acid residues 1-29 are involved in translocation of C2I but are not absolutely essential for binding to C2IIa... - Salmonella enterica SpvB ADP-ribosylates actin at position arginine-177-characterization of the catalytic domain within the SpvB protein and a comparison to binary clostridial actin-ADP-ribosylating toxinsHenrike Hochmann
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, D-79104 Freiburg, Germany
Biochemistry 45:1271-7. 2006..The maximal reaction rates were comparable for all toxins, whereas variable K(m) values for NAD were evident. We identified arginine-177 as the modification site for C/SpvB with the actin homologue protein Act88F from Drosophila... - The host cell chaperone Hsp90 is necessary for cytotoxic action of the binary iota-like toxinsGerd Haug
, , D-79104 Freiburg, Germany
Infect Immun 72:3066-8. 2004..Inhibition of Hsp90 by its specific inhibitor radicicol delayed intoxication of Vero cells by these toxins. A common Hsp90-dependent mechanism for their translocation is discussed... - Clostridium botulinum C2 toxin: low pH-induced pore formation is required for translocation of the enzyme component C2I into the cytosol of host cellsDagmar Blöcker
Institut fur Experimentelle und Klinische Pharmakologie, Albertstrasse 25, Otto Krayer Haus, D 79104 Freiburg, Germany
J Biol Chem 278:37360-7. 2003..Intoxication of target cells with C2 toxin requires a strictly coordinated pH-dependent sequence of binding, pore formation by C2IIa, and translocation of C2I... - Characterization of the enzymatic component of the ADP-ribosyltransferase toxin CDTa from Clostridium difficileI Gülke
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, D 79104 Freiburg, Germany
Infect Immun 69:6004-11. 2001..The enzyme components of CDT, iota toxin, and C2 toxin differ with respect to the minimal structural requirement for full enzyme activity... - Clostridium botulinum C2 toxin delays entry into mitosis and activation of p34cdc2 kinase and cdc25-C phosphatase in HeLa cellsH Barth
Institut für Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, D 79104 Freiburg, Germany
Infect Immun 67:5083-90. 1999.... - Rho GTPases and phosphoinositide 3-kinase organize formation of branched dendritesJost Leemhuis
Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat, Freiburg, Germany
J Biol Chem 279:585-96. 2004..The present results show a central role of phosphoinositide 3-kinases in dendrite formation. In neuronal cells, increased levels of cAMP can support dendritic arborization by modulating the activity of the lipid kinase... - Interaction of the Rho-ADP-ribosylating C3 exoenzyme with RalAChristian Wilde
, Otto-Krayer-Haus, Albertstrasse 25, D-79104 Freiburg, Germany
J Biol Chem 277:14771-6. 2002..The data indicate that several C3 exoenzymes directly interact with RalA without ADP-ribosylating the GTPase. The interaction is of high affinity and interferes with essential functions of C3 and RalA... - Mechanism of C2-toxin inhibition by fluphenazine and related compounds: investigation of their binding kinetics to the C2II-channel using the current noise analysisChristoph Bachmeyer
CNR-ITC Istituto di Biofisica-Sezione di Trento, Via Sommarive 18, I-38050, Povo, Italy
J Mol Biol 333:527-40. 2003..The off-rate varied between about 10 s(-1) and 3900 s(-1) and depended on the structure of the ligand. The role of structural requirements for the effective block of C2II by the different ligands is discussed... - Binary actin-ADP-ribosylating toxins and their use as molecular Trojan horses for drug delivery into eukaryotic cellsHolger Barth
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert Einstein Allee 11, D 89081 Ulm, Germany
Curr Med Chem 15:459-69. 2008..This review will focus on the recent progress in studying binary actin ADP-ribosylating toxins as highly effective virulence factors and innovative tools for cell physiology as well as pharmacology... - A cell-permeable fusion toxin as a tool to study the consequences of actin-ADP-ribosylation caused by the salmonella enterica virulence factor SpvB in intact cellsSascha Pust
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert Einstein Allee 11, D 89081 Ulm, Germany
J Biol Chem 282:10272-82. 2007..The acute cellular responses following ADP-ribosylation of actin did not immediately induce cell death of J774.A1 macrophage-like cells... - Formation of a biologically active toxin complex of the binary Clostridium botulinum C2 toxin without cell membrane interactionEva Kaiser
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert-Einstein-Allee 11, D-89081 Ulm, Germany
Biochemistry 45:13361-8. 2006..Intoxication of Vero cells and of human colon carcinoma cells (CaCo-2) was significantly enhanced when the preformed toxin complex was added to cultured cells as compared to addition of the single components... - Structure and action of the binary C2 toxin from Clostridium botulinumChristian Schleberger
, , Albertstr. 21, D-79104 Freiburg im Breisgau, Germany
J Mol Biol 364:705-15. 2006..It revealed a surprisingly large number of asparagine residues lining the pore. The interaction between C2-I and C2-IIa and the translocation of C2-I into the target cell are discussed... - Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra-Golgi pHFrancisco Lázaro-Diéguez
Departament de Biologia Cellular i Anatomia Patologica, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain
Cell Motil Cytoskeleton 63:778-91. 2006..This maintenance seems to be mediated by the regulation of the state of F-actin assembly on the Golgi pH homeostasis... - Purification and activity of the Rho ADP-ribosylating binary C2/C3 toxinGerd Haug
Albert Ludwigs Universitat Freiburg, Institut fur Experimentelle and Klinische Pharmakologie and Toxikologie, Germany
Methods Enzymol 406:117-27. 2006..This fusion toxin C2IN-C3 is transported into cells by interaction with the binding and translocation component (C2II) of C2 toxin. Purification and activity of the chimeric toxin is reported... - ADP-ribosylation of actin by the Clostridium botulinum C2 toxin in mammalian cells results in delayed caspase-dependent apoptotic cell deathKarin Heine
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany
Infect Immun 76:4600-8. 2008..From our data, we conclude that the long-lived nature of C2I in the host cell cytosol was essential for the nonreversible cytotoxic effect of C2 toxin, resulting in delayed apoptosis of the tested mammalian cells... - The host cell chaperone Hsp90 is essential for translocation of the binary Clostridium botulinum C2 toxin into the cytosolGerd Haug
, Albertstrasse 25 (Otto-Krayer-Haus, D-79104 Freiburg, Germany
J Biol Chem 278:32266-74. 2003..The data indicate that Hsp90 is essential for the membrane translocation of ADP-ribosylating toxins delivered by C2II... - Clostridium botulinum C2 toxin: binding studies with fluorescence-activated cytometryBradley G Stiles
Department of Immunology and Molecular Biology, US Army Medical Research Institute of Infectious Diseases, Frederick MD 21702 5011, USA
Toxicon 40:1135-140. 2002..Overall, these studies further demonstrated the utility of fluorescence-activated cytometry for studying the binding characteristics of bacterial binary toxins like C2... - Endothelial Rho signaling is required for monocyte transendothelial migrationAnke Strey
Institute of Medical Biochemistry, ZMBE, , , Germany
FEBS Lett 517:261-6. 2002..Thus, efficient leukocyte extravasation requires Rho signaling not only within the migrating leukocytes but also within the endothelial lining of the vessel wall... - Inhibition of Rac GTPase triggers a c-Jun- and Bim-dependent mitochondrial apoptotic cascade in cerebellar granule neuronsShoshona S Le
Research Service, Veterans Affairs Medical Center, Denver, Colorado 80220, USA
J Neurochem 94:1025-39. 2005..These results indicate that Rac acts downstream of integrins and growth factors to promote neuronal survival by repressing c-Jun/Bim-mediated mitochondrial apoptosis... - Listeria monocytogenes induced Rac1-dependent signal transduction in endothelial cellsBernd Schmeck
Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charit, , Augustenburger Platz 1, 13353 Berlin, Germany
Biochem Pharmacol 72:1367-74. 2006..In conclusion, Rac1 contributed to L. monocytogenes-induced cytokine expression by human endothelial cells... - Rho family GTPase inhibition reveals opposing effects of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and Janus kinase/signal transducer and activator of transcription signaling cascades on neuronal survivalF Alexandra Loucks
Research Service, Veterans Affairs Medical Center, Denver, Colorado 80220, USA
J Neurochem 97:957-67. 2006..These data suggest that the MEK/ERK cascade functions downstream of Rac GTPase to actively repress pro-apoptotic JAK/STAT signaling in healthy CGNs... - Difference in the cytotoxic effects of toxin B from Clostridium difficile strain VPI 10463 and toxin B from variant Clostridium difficile strain 1470Johannes Huelsenbeck
Institut of Toxicology, Medical School, Hannover, D 30625 Hannover, Germany
Infect Immun 75:801-9. 2007..In conclusion, the protein substrate specificity of the glucosylating toxins determines their biological activity... - Oxidized LDL and its compound lysophosphatidylcholine potentiate AngII-induced vasoconstriction by stimulation of RhoAJan Galle
Department of Medicine, Julius Maximilians Universitat, Wurzburg, Germany
J Am Soc Nephrol 14:1471-9. 2003..Lysophosphatidylcholine mimics the OxLDL effect, consistent with a causal role of this OxLDL compound. Stimulation of RhoA by OxLDL may contribute to vasospasm in atherosclerotic arteries... - Downregulation of protein phosphatase 2A activity in HeLa cells at the G2-mitosis transition and unscheduled reactivation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA)Manuela Klingler-Hoffmann
Former Department of Pathochemistry, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Eur J Cell Biol 84:719-32. 2005..The results suggest that the activity of cellular PP2A requires downregulation for the transition from G2 phase to mitosis. Unscheduled reactivation of PP2A induced by TPA in late G2 phase appears to inhibit the progress into mitosis... - Role of Rac and Cdc42 in lysophosphatidic acid-mediated cyclo-oxygenase-2 gene expressionAngelika Hahn
Medizinische Klinik IV, Universitat Erlangen Nurnberg, Loschgestr 8, D 91054 Erlangen, Germany
Biochem J 362:33-40. 2002..By exclusion of RhoA and non-specific cytoskeletal effects, the results in the present study indicate an important role for Rac and/or Cdc42 in pertussis toxin-sensitive LPA-mediated Cox-2 induction...