Botulinum Neurotoxin and Tetanus Toxin

Botulinum Neurotoxin and Tetanus Toxin covers the mechanism of action, pathogenesis, and treatment of clostridial neurotoxins. The book is organized into four parts encompassing 18 chapters that discuss the origin, structure, pharmacology, toxicology, immunology, assays, and clinical issues of botulinum and tetanus neurotoxins. The introductory part of the book discusses the discovery and production of neurotoxins in various strains of Clostridium bacteria. This text also describes how specific bacteriophages and plasmids mediate the pathogenicity of some types of Clostridium botulinum and Clostridium tetani. The subsequent part provides an overview of issues related to toxin binding, including toxins that may serve as models for botulinum and tetanus neurotoxins. Discussions on the peripheral and central aspects of poisoning transport in the central nervous system and on the antagonistic drugs for clostridial neurotoxins are provided. The third part of the book addresses the antibodies against botulinum neurotoxin. Bioassay in mice and highly sensitive immunoassays, such as reversed passive hemagglutination, reversed passive latex agglutination, radioimmunoassay, and enzyme-linked immunosorbent assay, are presented. The concluding part covers the animal models for these toxins and discusses the diagnosis and treatment of botulism and tetanus in human. The clinical use of Clostridium botulinum toxin type A in ocular and neuromuscular disease is also examined. This book will be of value to protein chemists, microbiologists, virologists, pharmacologists, immunologists, and clinicians.

Contributors PrefaceI. Origin and Structure 1. Bacterial Sources of Clostridial Neurotoxins I. Introduction II. Discovery of Neurotoxigenic Clostridia III. Organisms That Produce Botulinum Neurotoxin IV. Organisms That Produce Tetanus Neurotoxin V. Final Considerations References 2. Bacteriophages and Plasmids in Clostridium botulinum and Clostridium tetani and Their Relationship to Production of Toxins I. Introduction II. General Characteristics of Bacteriophages and Their Bacterial Host III. Bacteriophages of Clostridium botulinum Group III and Their Relationship to Neurotoxin Production IV. Relationship of Phages to Production of Neurotoxin by Other Groups of Clostridium botulinum V. Plasmids and Their Role in Toxigenicity of Clostridium botulinum VI. Relationship of Phages to Production of Neurotoxin by Clostridium tetani VII. Plasmids and the Toxigenicity of Clostridium tetani VIII. Concluding Statements References 3. The Structure of Botulinum Neurotoxin I. Macrostructure of Botulinum Neurotoxin II. Chemical Structure of the Neurotoxin III. Conformation (Secondary and Tertiary Structure) of the Neurotoxin IV. Structural Domains V. Endogenous Conversion of the Single to Dichain Neurotoxin VI. Probable Cause of Activation References 4. The Structure of Tetanus Toxin I. Introduction II. Nomenclature III. Gross Structure of the Molecule IV. Primary Structure V. Secondary Structure VI. Antigenic Substructure VII. Similarities between Tetanus and Botulinum Neurotoxin Molecules VIII. Concluding Remarks References II. Pharmacology and Toxicology 5. Cell Surface Receptors for Protein Toxins I. Introduction II. Receptor Biochemistry III. Microbial Toxin Receptors References 6. Entry of Bacterial Toxins into Mammalian Cells I. Introduction II. Receptor-Mediated Endocytosis III. Inhibition of Receptor-Mediated Endocytosis IV. Entry of Diphtheria and Pseudomonas Toxins into Mammalian Cells V. Entry of Botulinum Neurotoxins and Tetanus Toxin into Mammalian Cells References 7. Peripheral Actions of the Botulinum Toxins I. Introduction II. Summarizing the Model for Neurotoxin Action III. Tissue Binding IV. Internalization of Neurotoxin V. Mechanism of Neurotoxin Action VI. Clostridial Binary Toxins References 8. Peripheral Actions of Tetanus Toxin I. Introduction and Historical Perspective II. Neuromuscular Transmission III. Exocytosis of Adrenergic Transmitter IV. Comparison of Action of Tetanus Toxin and Botulinum Toxins V. Concluding Remarks References 9. Axoplasmic Transport and Transynaptic Movement of Tetanus Toxin I. Introduction II. Toxin Fixation III. Internalization of Bound Tetanus Toxin IV. Retrograde Transport of the Toxin V. Transynaptic Movement of Tetanus Toxin VI. Relationships between Transport and Biological Activity of Tetanus Toxin VII. Use of Tetanus Toxin-Derived Fragments as Specific Carriers for Drugs to the CNS VIII. Retrograde Transport and Neurotropism References 10. Clostridial Toxins and the Central Nervous System: Studies on In Situ Tissues I. Spinal and Supraspinal Neurons of Arrival for Tetanus and Botulinum Toxins II. Actions of the Toxins on the Function and Structure of the Neurons of Arrival III. Transsynaptic Transport of Tetanus Toxin IV.