Clostridial Neurotoxins

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Clostridial Neurotoxins

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Author : Cesare Montecucco
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-11-11

Clostridial Neurotoxins written by Cesare Montecucco and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-11 with Medical categories.

Tetanus has been known from the very beginning of medical literature since it was first described by Hyppocrates of Cos in the fifth century B.C. For 24 centuries it was considered a neuro logical disease until the breakthrough of CARLE and RATIONE (1884) who demonstrated its infectious etiology. Following the establishment of purified cultures of Clostridium tetani(KITASATO 1889), FABER (1890), and TIZZONI and CATIANI (1890) demon strated that the disease is actually an intoxication caused by a proteic neurotoxin. This toxin was shown by BRUSHCHETIINI (1892) to move retroaxonally and to act at the spinal cord level. Soon thereafter VAN ERMENGEN (1897) demonstrated that botu lism is also due to intoxication with a protein toxin produced by bacteria of the genus Clostridium. These bacteria and their spores and ubiquitous, and the majority of them do not produce neurotoxins. The selective advantage of producing such potent toxin is still a matter of speculation (see Popoff, this volume). The next major advance was the discovery that tetanus neurotoxin 1 can be converted by formaldehyde treatment to a nonpathogenic but still fully immunogenic form, and that this can be used successfully as a vaccine to prevent tetanus (RAMON and DESCOMBEY 1925). Similar vaccines (toxoids) can be prepared with botulism neurotoxins (see MiDDLEBROOK and BROWN, this volume). The prevention oftetanus by vaccination (see Galatzka and Gasse, this volume) is one of the great successes of basic research coupled with an efficient public medicine service.

Treatments From Toxins

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Author : Keith Alan Foster
language : en
Publisher: CRC Press
Release Date : 2006-11-02

Treatments From Toxins written by Keith Alan Foster and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006-11-02 with Medical categories.

As little as two decades ago, deliberately injecting botulinum toxin into patients would have seemed foolhardy at best and criminal at worst. The increased clinical use of botulinum toxins has expanded the body of knowledge available on the structure and function of these proteins. This knowledge can be applied to topics as varied as therapies base

Botulinum Neurotoxin And Tetanus Toxin

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Author : Lance Simpson
language : en
Publisher: Elsevier
Release Date : 2012-12-02

Botulinum Neurotoxin And Tetanus Toxin written by Lance Simpson and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-02 with Medical categories.

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.

Botulinum And Tetanus Neurotoxins

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Author : B.R. DasGupta
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-11-11

Botulinum And Tetanus Neurotoxins written by B.R. DasGupta and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-11 with Medical categories.

Three days in Madison have thoroughly modified my view on clostridial neurotoxins. While still realizing the numerous activating, modifying and protective inputs, I cannot judge the meaningfulness of the meeting impartially. Neither may the reader expect a complete summary of all presentations. Collected in this volume, they speak for themselves without requiring an arbiter. Instead I shall write down my very personal opinions as a researcher who has studied clostridial neurotoxins for nearly 25 years. Comparable conferences have been rare during this time. A comprehensive symposium 4 on C. botulinum neurotoxins has been organized at Ft. Detrick. International conferences on tetanus have been held regularly under the auspices of the Wodd Health Organization. One or maximally two days of these meetings have been devoted to tetanus toxin and its actions whereas the sponsor and the majority of the participants have been interested mainly in epidemiology, prevention and treatment of tetanus as a disease (see refs. 5,6). Some aspects of clostridial neurotoxins have been addressed in the context of bacterial toxins, in particular in the biennial European workshops. 1-3,7,8 The Madison meeting differed from the previous ones in three aspects. First, it covered both tetanus and botulinum neurotoxins. The fusion was justified because of their huge similarities in primary structure, in their mode of action and in their cellular targets. Second, the meeting was not limited to toxins but drew some lines on which modern neurobiology might proceed.

Botulinum Neurotoxins

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Author : Andreas Rummel
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-14

Botulinum Neurotoxins written by Andreas Rummel and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-14 with Medical categories.

The extremely potent substance botulinum neurotoxin (BoNT) has attracted much interest in diverse fields. Originally identified as cause for the rare but deadly disease botulism, military and terrorist intended to misuse this sophisticated molecule as biological weapon. This caused its classification as select agent category A by the Centers for Diseases Control and Prevention and the listing in the Biological and Toxin Weapons Convention. Later, the civilian use of BoNT as long acting peripheral muscle relaxant has turned this molecule into an indispensable pharmaceutical world wide with annual revenues >$1.5 billion. Also basic scientists value the botulinum neurotoxin as molecular tool for dissecting mechanisms of exocytosis. This book will cover the most recent molecular details of botulinum neurotoxin, its mechanism of action as well as its detection and application.

Physiological And Alternative Entry Pathways Of The Clostridial Neurotoxins

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Author : Felix L. Yeh
language : en
Publisher:
Release Date : 2011

Physiological And Alternative Entry Pathways Of The Clostridial Neurotoxins written by Felix L. Yeh and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.

Functional And Evolutionary Insights Into Botulinum Neurotoxins And Homologous Toxins

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Author : Travis Gwynn Wentz
language : en
Publisher:
Release Date : 2023

Functional And Evolutionary Insights Into Botulinum Neurotoxins And Homologous Toxins written by Travis Gwynn Wentz and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023 with categories.

Classical clostridial neurotoxins including tetanus neurotoxin and seven antigenically distinct serotypes of botulinum neurotoxin are potent proteinaceous toxins composed of three functional domains. Responsible for the paralytic diseases tetanus and botulism, the clostridial neurotoxin family is produced by multiple species of Clostridium and localizes to plasmids, bacteriophage, and the bacterial chromosome suggestive of a deep history of horizontal gene transfer. In Group I Clostridium botulinum, the species responsible for most human foodborne botulism cases, three serotypes of botulinum neurotoxins occur both within a family of large conjugative plasmids and at discrete sites within the chromosome. To further understand the transfer and localization of these toxins in Group I C. botulinum, a bioinformatic survey of CRISPR-Cas systems was conducted to test whether these endogenous genomic defense complexes play a potential role regulating toxin transfer at the species level. No evidence was found for direct targeting of botulinum neurotoxin associated genes by CRISPR-Cas systems, but CRISPR-Cas systems were predicted to frequently target botulinum neurotoxin producing, conjugative plasmids. Further, these plasmids themselves were found to possess a unique nuclease deficient variant of the type I-B CRISPR-Cas system, which could play roles in plasmid incompatibility, maintenance, and survival. Coupled with the high frequency of chromosomally localized type I and III CRISPR-Cas systems, these results indicate that CRISPR-Cas systems are tolerant of botulinum toxins as an accessory gene product but may nonetheless play a significant role in the regulation of their trafficking throughout Group I C. botulinum. Since 2015, a fast-growing outgroup of botulinum-like toxins have been identified in diverse bacterial species within and beyond genus Clostridium. These homologous toxins possess comparable domain structures to clostridial neurotoxins and are frequently conserved at key functional motifs capable of enzymatically cleaving known botulinum substrates. These attributes make them excellent tools for exploring the evolution of clostridial neurotoxins and may additionally confer unique and pharmacologically desirable activities. However, their capacity to cause disease akin to tetanus or botulism at similar potency to the classical toxin family remains largely unknown. Recombinant expression of a botulinum-like toxin from Enterococcus demonstrated a capacity to cause botulism in mice, though this required a significantly larger quantity of toxin relative to the classical neurotoxin serotypes. Chimeric constructs composed of the enzymatic and translocative domains of the botulinum-like toxin and binding domain of botulinum serotype A was intermediately toxic between the two. These findings coupled with mixed toxicity results from additional botulinum-like toxins indicates botulinum-like toxins vary significantly in mammalian potency and function, requiring investigation on a case-by-case basis.

The Clostridia

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Author : Julian I. Rood
language : en
Publisher: Academic Press
Release Date : 1997-04-30

The Clostridia written by Julian I. Rood and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1997-04-30 with Science categories.

The clostridia are a group of bacteria of considerable medical and economic importance and include species responsible for generating the most potent toxins known to humans. The Clostridia: Molecular Biology and Pathogenesis is a unique work, comprising the most complete reference on the clostridia for over 20 years, bringing together the results from some of the most innovative and exciting research in the past decade. Using a principle-oriented rather than taxonomic approach, the results from molecular biology research are placed in the context of their clinical significance, and the disease process as a whole. This state-of-the-art work is truly comprehensive, covering and integrating the diverse topics of genetics, physiology, pathogenesis and cell biology. Written and edited by world-renowned authorities, material is presented to give the reader an up-to-date knowledge of the pathogenic species of this important genus. Background information is followed by details of the genetics, molecular biology, biochemistry and disease mechanisms. The structure, function and mode of action of toxins and other virulence determinants is clearly presented. As such, this work will prove essential for students, teachers, research microbiologists, infectious disease clinicians, toxin specialists, and all those working in medical or veterinary bacteriology, microbial genetics and the pharmaceutical industries. Covers appropriate medical and veterinary topics Contains authoritative contributions by international experts Presents the current state of knowledge and areas for future research Truly comprehensive--covers topics from molecular biology and physiology

Molecular Aspects Of Botulinum Neurotoxin

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Author : Keith A. Foster
language : en
Publisher: Springer
Release Date : 2014-07-08

Molecular Aspects Of Botulinum Neurotoxin written by Keith A. Foster and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-07-08 with Science categories.

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation with a focus on clinical application. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

Handbook Of Neurotoxicology

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Author : Edward J. Massaro
language : en
Publisher: Springer Science & Business Media
Release Date : 2001-11-12

Handbook Of Neurotoxicology written by Edward J. Massaro and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001-11-12 with Medical categories.

Neurotoxicology is a broad and burgeoning field of research. Its growth in recent years can be related, in part, to increased interest in and concern with the fact that a growing number of anthropogenic agents with neurotoxic potential, including pesticides, lead, mercury, and the polytypic bypro ducts of combustion and industrial production, continue to be spewed into and accumulate in the environment. In addition, there is great interest in natural products, including toxins, as sources of therapeutic agents. Indeed, it is well known that many natural toxins of broadly differing structure, produced or accumulated for predatory or defensive purposes, and toxic agents, accumulated incidentally by numerous species, function to perturb nervous tissue. Components of some of these toxins have been shown to be useful therapeutic agents and/or research reagents. Unfor tunately, the environmental accumulation of some neurotoxic ants of anthropogenic ori gin, especially pesticides and metals, has resulted in incidents of human poisoning, some of epidemic proportion, and high levels of morbidity and mortality. Furthermore, an increasing incidence of neurobehavioral disorders, some with baffling symptoms, is confronting clinicians. It is not clear whether this is merely the result of increased vigi lance and/or improved diagnostics or a consequence of improved health care. In any case, the role of exposure to environmental and occupational neurotoxic ants in the etiology of these phenomena, as well as neurodegenerative diseases, is coming under increasing scrutiny and investigation.