Functional And Evolutionary Insights Into Botulinum Neurotoxins And Homologous Toxins
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Functional And Evolutionary Insights Into Botulinum Neurotoxins And Homologous Toxins
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Author : Travis Gwynn Wentz (Ph.D.)
language : en
Publisher:
Release Date : 2023
Functional And Evolutionary Insights Into Botulinum Neurotoxins And Homologous Toxins written by Travis Gwynn Wentz (Ph.D.) 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.
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.
Biological Toxins And Bioterrorism
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Author : P. Gopalakrishnakone
language : en
Publisher: Springer
Release Date : 2015-01-22
Biological Toxins And Bioterrorism written by P. Gopalakrishnakone and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-01-22 with Medical categories.
Biological toxins are an important part of our world, a reality with which we need to cope, so in parallel with understanding their mechanisms of action and thereby improving our fundamental knowledge, there are successful efforts to utilize them as therapeutics against some debilitating human and animal diseases. In view of the complexity of different types of biotoxins and the broad range of toxin structure, physiology, utility, and countermeasures including regulatory issues, it was thus aimed to compile a book on biotoxins and bioweapons. This reference work in the Toxinology handbook series gathers together knowledge from around the globe about naturally inspired and manufactured biological weapons. The authors describe how they work; how authorities may detect their presence, prevent their use, and diagnose their impacts; and the means by which medical and paramedical professionals may treat victims. Also described are how they have been used to further our knowledge and what insights they have given us into evolutionary and physiological processes. Finally, it is also discussed how these toxins can be used as therapeutics and what the implications of such therapeutics are to their use as biothreat agents. This volume provides a reference accessible to scientists, educators, and medical experts alike with an interest in biotoxins, focusing on the major toxins used as bioweapons. Regulatory agencies will also benefit from the information provided in this book. Some in the intended audience may need to understand how they elicit their effects and how we can defend ourselves against them. Others may be interested in the sometimes colorful histories that surround this subset of biotoxins that can be and, in some cases, have been used as weapons.
Botulinum Neurotoxins
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Author : Andreas Rummel
language : en
Publisher: Springer
Release Date : 2015-01-29
Botulinum Neurotoxins written by Andreas Rummel and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-01-29 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.
Botulinum And Tetanus Neurotoxins
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Author : B. R. Dasgupta
language : en
Publisher:
Release Date : 2014-01-15
Botulinum And Tetanus Neurotoxins written by B. R. Dasgupta and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-01-15 with categories.
Clostridial Diseases Of Animals
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Author : Francisco A. Uzal
language : en
Publisher: John Wiley & Sons
Release Date : 2016-05-31
Clostridial Diseases Of Animals written by Francisco A. Uzal and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-05-31 with Medical categories.
Clostridial Diseases of Animals is the first book to focus on clostridial diseases in domestic and wild animals, offering a comprehensive reference on these common diseases. Provides a single resource for all aspects of clostridial diseases Presents current, comprehensive information with a focus on clinical relevance Covers each disease in depth, including etiology, epidemiology, clinics, gross pathology, histopathology, diagnostics, diagnostic criteria, prophylaxis, control, and treatment Written by the world-leading experts in the field of clostridial diseases in animals Offers photographs and summary tables to support the concepts discussed in the text and aid in recognition
Toxins In Drug Discovery And Pharmacology
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Author : Steve Peigneur
language : en
Publisher: MDPI
Release Date : 2018-05-04
Toxins In Drug Discovery And Pharmacology written by Steve Peigneur and has been published by MDPI this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-05-04 with Drug categories.
This book is a printed edition of the Special Issue "Toxins in Drug Discovery and Pharmacology" that was published in Toxins
Protein Toxins In Modeling Biochemistry
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Author : Raj Kumar
language : en
Publisher: Springer
Release Date : 2016-11-21
Protein Toxins In Modeling Biochemistry written by Raj Kumar and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-11-21 with Science categories.
This succinct volume addresses the production of inactive, potentially toxic proteins in the absence of correct protein folding and the resultant neurodegenerative diseases. Other topics include intrinsic disorder in protein structure and function and the effects of molten globules on protein toxicity. This concise and yet thorough text also discusses using toxin structure as a model for studying structural and functional aspects of protein chemistry. Protein Toxins in Modeling Biochemistry, a SpringerBrief, is essential reading for advanced researchers, scientists and advanced graduate students interested in protein chemistry and related areas of biochemistry and molecular science.
Botulism In The United States 1899 1973
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Author : United States. Public Health Service
language : en
Publisher:
Release Date : 1974
Botulism In The United States 1899 1973 written by United States. Public Health Service and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1974 with Botulism categories.
The Pangenome
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Author : Hervé Tettelin
language : en
Publisher: Springer Nature
Release Date : 2020-04-30
The Pangenome written by Hervé Tettelin and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-04-30 with Science categories.
This open access book offers the first comprehensive account of the pan-genome concept and its manifold implications. The realization that the genetic repertoire of a biological species always encompasses more than the genome of each individual is one of the earliest examples of big data in biology that opened biology to the unbounded. The study of genetic variation observed within a species challenges existing views and has profound consequences for our understanding of the fundamental mechanisms underpinning bacterial biology and evolution. The underlying rationale extends well beyond the initial prokaryotic focus to all kingdoms of life and evolves into similar concepts for metagenomes, phenomes and epigenomes. The book’s respective chapters address a range of topics, from the serendipitous emergence of the pan-genome concept and its impacts on the fields of microbiology, vaccinology and antimicrobial resistance, to the study of microbial communities, bioinformatic applications and mathematical models that tie in with complex systems and economic theory. Given its scope, the book will appeal to a broad readership interested in population dynamics, evolutionary biology and genomics.