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33 results on '"Rummel, Andreas"'

1. Design and Production of Full-Length, Biologically Inactive Botulinum Neurotoxin Serotypes to Serve as Natively Folded Antigens for Antitoxin Generation

Author

Modenbach, Jana Marielle, primary, Klepka, Carmen, additional, Weisemann, Jasmin, additional, Przykopanski, Adina, additional, Josuran, Roland, additional, Hobi, Patrizia, additional, Koller, Angelika, additional, Marechal, Maud, additional, Nahori, Marie-Anne, additional, Stevenn, Volant, additional, Gerber, Sabina M., additional, Lemichez, Emmanuel, additional, and Rummel, Andreas, additional

Published
2024
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7. Inhibiting oral intoxication of botulinum neurotoxin A complex by carbohydrate receptor mimics

Author

Lee, Kwangkook, Lam, Kwok-Ho, Kruel, Anna-Magdalena, Mahrhold, Stefan, Perry, Kay, Cheng, Luisa W, Rummel, Andreas, and Jin, Rongsheng

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Foodborne Illness, Vaccine Related, Prevention, Biodefense, Digestive Diseases, Infectious Diseases, Emerging Infectious Diseases, Oral and gastrointestinal, Administration, Oral, Animals, Botulinum Toxins, Type A, Botulism, Caco-2 Cells, Crystallography, X-Ray, Female, Hemagglutinins, Humans, Isopropyl Thiogalactoside, Lactulose, Mice, Protein Binding, Botulinum neurotoxin, Hemagglutinin, Progenitor toxin complex, Carbohydrate receptor, Inhibitor, Pharmacology and Pharmaceutical Sciences, Toxicology, Biochemistry and cell biology, Immunology, Pharmacology and pharmaceutical sciences
Abstract

Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes for botulism. BoNT assembles with several auxiliary proteins to survive in the gastrointestinal tract and is subsequently transported through the intestinal epithelium into the general circulation. Several hemagglutinin proteins form a multi-protein complex (HA complex) that recognizes host glycans on the intestinal epithelial cell surface to facilitate BoNT absorption. Blocking carbohydrate binding to the HA complex could significantly inhibit the oral toxicity of BoNT. Here, we identify lactulose, a galactose-containing non-digestible sugar commonly used to treat constipation, as a prototype inhibitor against oral BoNT/A intoxication. As revealed by a crystal structure, lactulose binds to the HA complex at the same site where the host galactose-containing carbohydrate receptors bind. In vitro assays using intestinal Caco-2 cells demonstrated that lactulose inhibits HA from compromising the integrity of the epithelial cell monolayers and blocks the internalization of HA. Furthermore, co-administration of lactulose significantly protected mice against BoNT/A oral intoxication in vivo. Taken together, these data encourage the development of carbohydrate receptor mimics as a therapeutic intervention to prevent BoNT oral intoxication.

Published
2015

20. Toxins 2017 conference in Madrid

Author

Albanese, Alberto, primary, Cardoso, Francisco, additional, Fujinaga, Yukako, additional, Jankovic, Joseph, additional, Rummel, Andreas, additional, and Schiavo, Giampietro, additional

Published
2018
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23. Detection and differentiation of botulinum neurotoxin serotypes C, D, and their mosaic variants by highly specific immunoassays and mass spectrometry

Author

Hansbauer, Eva-Maria, primary, Skiba, Martin, additional, Endermann, Tanja, additional, Stern, Daniel, additional, Dorner, Martin B., additional, Finkenwirth, Friedrich, additional, Wolf, Jessica, additional, Luginbühl, Werner, additional, Rummel, Andreas, additional, Messelhäusser, Ute, additional, Bellanger, Laurent, additional, Woudstra, Cédric, additional, Fach, Patrick, additional, and Dorner, Brigitte G., additional

Published
2016
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26. 124. Isolation and functional characterization of the novel Clostridium botulinum A8 neurotoxin subtype

Author

Kull, Skadi, primary, Schulz, Melanie, additional, Weisemann, Jasmin, additional, Kirchner, Sebastian, additional, Schreiber, Tanja, additional, Bollenbach, Alexander, additional, Dabrowski, Wojtek, additional, Nitsche, Andreas, additional, Kalb, Suzanne, additional, Dorner, Martin, additional, Barr, John, additional, Rummel, Andreas, additional, and Dorner, Brigitte, additional

Published
2015
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32. Characterising and exploiting the binding of botulinum neurotoxins to their neuronal receptors

Author

Bigalke Hans, Karnath Tino, Häfner Kirstin, Mahrhold Stefan, Rummel Andreas, and Binz Thomas

Subjects
Ganglioside binding, Neurotoxin, Binding site, Biology, Toxicology, Endocytosis, Receptor, Molecular biology, Synaptic vesicle, Synaptotagmin 1, Exocytosis
Abstract

Botulinum neurotoxins (BoNT) cause muscle paralysis by inhibiting the exocytosis at motor nerve terminals. Initially, they bind to abundant complex polysialogangliosides via a conserved pocket within the C-terminal half of their cell binding domain (Hcc-domain). Engineering of this binding site in BoNT/A leads to mutants with >3-fold increased potency, which can be exploited as new therapeutics with decreased dosage and thus might prolong the period until immune response in patients. Additionally, protein receptors are required for productive neurotoxin uptake. While BoNT/B and G share the synaptic vesicle proteins synaptotagmin (Syt) I and Syt-II as protein receptors, BoNT/A uniquely binds SV2. Recently, the interaction site of Syt I and Syt-II was located near the ganglioside binding pocket within the Hcc-domain of BoNT/B and G. Furthermore, the BoNT/B–Syt II interaction could be characterised at the atomic level. None of the so-far identified protein receptors interacts with BoNT/C, D, E, F and TeNT. Employing the ex vivo mouse phrenic nerve-hemidiaphragm as a physiological target, the type and number of unknown neurotoxin receptor candidates were narrowed down. The productive uptake of BoNT/C, D, E and F is stimulation dependent, which points towards receptors being part of synaptic vesicles. Moreover, the endocytosis of BoNT/C, E and F, is inhibited by addition of any Hc-fragment derived from BoNT/C, E and F, indicating a binding to the same receptor structures.

Published
2008

33. Inhibition of exocytotic activity in human mast cell line 1 by clostridial neurotoxin light chains

Author

Rummel Andreas, Mahrhold Stefan, Balletta Andrea, Bigalke Hans, Schlesinger Friedrich, Binz Thomas, and Gui Daniele

Subjects
medicine.medical_treatment, Degranulation, Biology, Toxicology, Mast cell, Exocytosis, Cell biology, Interleukin 33, Cytokine, medicine.anatomical_structure, Cytoplasm, medicine, Secretion, Intracellular
Abstract

The main object of this work is to deliver the catalytically active portion of neurotoxins (light chain) into the cytosol of mast cells to inhibit the specific release of inflammatory mediators. Mast cells play a significant role in the pathophysiology of many different diseases. In most of these diseases there is increased recruitment of mast cells and sustained secretion of many proinflammatory mediators, including autacoids, cytokines and proteases. We use the human mast cell line 1 (HMC-1), a leukaemia line expressing several features of mature human mast cells that has proved a valuable model for studying human mast cell biology. In order to stimulate fusion among secretory granules, we use intracellular application of GTPgammaS and extracellular stimulation with concanavalin A. By patch-clamp technique, we determine the changes in cell membrane capacitance, thereby studying exocytosis. The whole-cell configuration of patch-clamp is used. By electroporation, the light chains of TeNT and BoNT/C & D will be delivered into the cytoplasm of mast cells to estimate their effects on mast cell activity. Cells treated with neurotoxins will be subjected to stimulation tests “in vitro”, recording of membrane capacitance by patch-clamp and detection of cytokine release to estimate effects on mast cell activity.

Published
2008

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