H Barth

Summary

Affiliation: University of Freiburg
Country: Germany

Publications

  1. pmc Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins
    Holger 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
  2. ncbi request reprint The uptake machinery of clostridial actin ADP-ribosylating toxins--a cell delivery system for fusion proteins and polypeptide drugs
    Holger 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
  3. ncbi request reprint Uptake of binary actin ADP-ribosylating toxins
    H 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
  4. ncbi request reprint Cellular uptake of Clostridium difficile toxin B. Translocation of the N-terminal catalytic domain into the cytosol of eukaryotic cells
    Gunther Pfeifer
    Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, Otto Krayer Haus, Albertstrasse 25, D 79104 Freiburg, Germany
    J Biol Chem 278:44535-41. 2003
  5. ncbi request reprint Cellular uptake of Clostridium botulinum C2 toxin: membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domain
    Gerd Haug
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, Germany
    Biochemistry 42:15284-91. 2003
  6. ncbi request reprint 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 vivo
    Dagmar 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
  7. pmc Cellular uptake of the Clostridium perfringens binary iota-toxin
    D Blocker
    Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, D 79104 Freiburg, Germany
    Infect Immun 69:2980-7. 2001
  8. ncbi request reprint Hypereosinophilia induced by high-dose intratumoral and peritumoral mistletoe application to a patient with pancreatic carcinoma
    R Huber
    Center for Complementary Medicine, Department of Gastroenterology, University of Freiburg, Germany
    J Altern Complement Med 6:305-10. 2000
  9. ncbi request reprint Regulation of somatodendritic GABAA receptor channels in rat hippocampal neurons: evidence for a role of the small GTPase Rac1
    D K Meyer
    Department of Pharmacology, Albert Ludwigs University, 79104 Freiburg, Germany
    J Neurosci 20:6743-51. 2000
  10. ncbi request reprint Clostridium botulinum C2 toxin--new insights into the cellular up-take of the actin-ADP-ribosylating toxin
    Klaus Aktories
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, Freiburg, Germany
    Int J Med Microbiol 293:557-64. 2004

Collaborators

  • K Aktories
  • Dieter K Meyer
  • J Behlke
  • Michel R Popoff
  • R Klein
  • J Leemhuis
  • R Huber
  • Peter Sehr
  • B G Stiles
  • Jan Galle
  • Ralf Gerhard
  • S Gambaryan
  • M L Hale
  • Volker Gerke
  • Harald Genth
  • S S Bolz
  • Gerd Haug
  • Sascha Pust
  • Henrike Hochmann
  • Karin Heine
  • Christoph Bachmeyer
  • Dagmar Blöcker
  • Eva Kaiser
  • F Alexandra Loucks
  • Shoshona S Le
  • Roland Benz
  • Christian Wilde
  • Johannes Huelsenbeck
  • Guido von Figura
  • Francisco Lázaro-Diéguez
  • Bernd Schmeck
  • Christian Schleberger
  • Daniel A Linseman
  • Manuela Klingler-Hoffmann
  • Ingo Just
  • Gunther Pfeifer
  • Angelika Hahn
  • Anke Strey
  • I Gülke
  • D Blocker
  • Stefanie Enzenmüller
  • Stefanie Dreger
  • Julia Eitel
  • Norbert Suttorp
  • Nuria Jimenez
  • Karolin Meixenberger
  • Abraham J Koster
  • Jaime Renau-Piqueras
  • Gudula Schmidt
  • Angela K Zimmermann
  • Marion Hliscs
  • Gustavo Egea
  • Georg E Schulz
  • Juan L Llopis
  • Kristen R Ryan
  • Trinad Chakraborty
  • Koert N J Burger
  • Vincent van Laak
  • Andreas C Hocke
  • Bastian Opitz
  • Stefan Hippenstiel
  • Wiebke Beermann
  • Kenneth L Tyler
  • Reid A Phelps
  • Sarah Richardson-Burns
  • Eric R Kandel
  • James Richards
  • Kim A Heidenreich
  • Norbert Konig
  • Hiroshi Udo
  • Volker Kinzel
  • Ron J Bouchard
  • Jörg Schirmer
  • Kathrin Pohlmann
  • Frank Orlik
  • Dirk Tiemann
  • Christian Busch
  • Margarete Goppelt-Struebe
  • Michaela Kress
  • Annette Janning
  • Martina Schmidt
  • Peter R Mertens
  • Li Han
  • G Pfeifer
  • J Liese
  • F Hofmann
  • M Fritz

Detail Information

Publications36

  1. pmc Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins
    Holger 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...
  2. ncbi request reprint The uptake machinery of clostridial actin ADP-ribosylating toxins--a cell delivery system for fusion proteins and polypeptide drugs
    Holger 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...
  3. ncbi request reprint Uptake of binary actin ADP-ribosylating toxins
    H 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...
  4. ncbi request reprint Cellular uptake of Clostridium difficile toxin B. Translocation of the N-terminal catalytic domain into the cytosol of eukaryotic cells
    Gunther Pfeifer
    Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, 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...
  5. ncbi request reprint Cellular uptake of Clostridium botulinum C2 toxin: membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domain
    Gerd Haug
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, 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...
  6. ncbi request reprint 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 vivo
    Dagmar 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...
  7. pmc Cellular uptake of the Clostridium perfringens binary iota-toxin
    D 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...
  8. ncbi request reprint Hypereosinophilia induced by high-dose intratumoral and peritumoral mistletoe application to a patient with pancreatic carcinoma
    R Huber
    Center for Complementary Medicine, Department of Gastroenterology, University of Freiburg, Germany
    J Altern Complement Med 6:305-10. 2000
    ..It is, however, still an open question whether this transient benefit was due to the induction of eosinophilia by a type-2 response...
  9. ncbi request reprint Regulation of somatodendritic GABAA receptor channels in rat hippocampal neurons: evidence for a role of the small GTPase Rac1
    D 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...
  10. ncbi request reprint Clostridium botulinum C2 toxin--new insights into the cellular up-take of the actin-ADP-ribosylating toxin
    Klaus 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...
  11. ncbi request reprint The binary Clostridium botulinum C2 toxin as a protein delivery system: identification of the minimal protein region necessary for interaction of toxin components
    Holger 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...
  12. ncbi request reprint 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 toxins
    Henrike 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...
  13. pmc The host cell chaperone Hsp90 is necessary for cytotoxic action of the binary iota-like toxins
    Gerd Haug
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, 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...
  14. ncbi request reprint Clostridium botulinum C2 toxin: low pH-induced pore formation is required for translocation of the enzyme component C2I into the cytosol of host cells
    Dagmar 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...
  15. pmc Characterization of the enzymatic component of the ADP-ribosyltransferase toxin CDTa from Clostridium difficile
    I 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...
  16. pmc Clostridium botulinum C2 toxin delays entry into mitosis and activation of p34cdc2 kinase and cdc25-C phosphatase in HeLa cells
    H Barth
    Institut für Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, D 79104 Freiburg, Germany
    Infect Immun 67:5083-90. 1999
    ....
  17. ncbi request reprint Rho GTPases and phosphoinositide 3-kinase organize formation of branched dendrites
    Jost 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...
  18. ncbi request reprint Interaction of the Rho-ADP-ribosylating C3 exoenzyme with RalA
    Christian Wilde
    Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, 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...
  19. ncbi request reprint Mechanism of C2-toxin inhibition by fluphenazine and related compounds: investigation of their binding kinetics to the C2II-channel using the current noise analysis
    Christoph 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...
  20. ncbi request reprint Binary actin-ADP-ribosylating toxins and their use as molecular Trojan horses for drug delivery into eukaryotic cells
    Holger 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...
  21. ncbi request reprint 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 cells
    Sascha 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...
  22. ncbi request reprint Formation of a biologically active toxin complex of the binary Clostridium botulinum C2 toxin without cell membrane interaction
    Eva 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...
  23. ncbi request reprint Structure and action of the binary C2 toxin from Clostridium botulinum
    Christian Schleberger
    Institut fur Organische Chemie und Biochemie, Albert Ludwigs Universitat, 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...
  24. ncbi request reprint Actin filaments are involved in the maintenance of Golgi cisternae morphology and intra-Golgi pH
    Francisco 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...
  25. ncbi request reprint Purification and activity of the Rho ADP-ribosylating binary C2/C3 toxin
    Gerd 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...
  26. pmc ADP-ribosylation of actin by the Clostridium botulinum C2 toxin in mammalian cells results in delayed caspase-dependent apoptotic cell death
    Karin 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...
  27. ncbi request reprint The host cell chaperone Hsp90 is essential for translocation of the binary Clostridium botulinum C2 toxin into the cytosol
    Gerd Haug
    Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert Ludwigs Universität Freiburg, 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...
  28. ncbi request reprint Clostridium botulinum C2 toxin: binding studies with fluorescence-activated cytometry
    Bradley 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...
  29. ncbi request reprint Endothelial Rho signaling is required for monocyte transendothelial migration
    Anke Strey
    Institute of Medical Biochemistry, ZMBE, University of Munster, Munster, 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...
  30. pmc Inhibition of Rac GTPase triggers a c-Jun- and Bim-dependent mitochondrial apoptotic cascade in cerebellar granule neurons
    Shoshona 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...
  31. ncbi request reprint Listeria monocytogenes induced Rac1-dependent signal transduction in endothelial cells
    Bernd Schmeck
    Department of Internal Medicine Infectious Diseases and Respiratory Medicine, Charite, Universitatsmedizin Berlin, 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...
  32. ncbi request reprint 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 survival
    F 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...
  33. pmc Difference in the cytotoxic effects of toxin B from Clostridium difficile strain VPI 10463 and toxin B from variant Clostridium difficile strain 1470
    Johannes 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...
  34. ncbi request reprint Oxidized LDL and its compound lysophosphatidylcholine potentiate AngII-induced vasoconstriction by stimulation of RhoA
    Jan 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...
  35. ncbi request reprint 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...
  36. pmc Role of Rac and Cdc42 in lysophosphatidic acid-mediated cyclo-oxygenase-2 gene expression
    Angelika 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...