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botulinum neurotoxin type A

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https://www.readbyqxmd.com/read/29050666/the-contribution-of-bacteriophages-to-the-biology-and-virulence-of-pathogenic-clostridia
#1
Louis-Charles Fortier
Bacteriophages are key players in the evolution of most bacteria. Temperate phages have been associated with virulence of some of the deadliest pathogenic bacteria. Among the most notorious cases, the genes encoding the botulinum neurotoxin produced by Clostridium botulinum types C and D and the α-toxin (TcnA) produced by Clostridium novyi are both encoded within prophage genomes. Clostridium difficile is another important human pathogen and the recent identification of a complete binary toxin locus (CdtLoc) carried on a C...
2017: Advances in Applied Microbiology
https://www.readbyqxmd.com/read/29033792/spontaneous-and-evoked-activity-from-murine-ventral-horn-cultures-on-microelectrode-arrays
#2
Bryan J Black, Rahul Atmaramani, Joseph J Pancrazio
Motor neurons are the site of action for several neurological disorders and paralytic toxins, with cell bodies located in the ventral horn (VH) of the spinal cord along with interneurons and support cells. Microelectrode arrays (MEAs) have emerged as a high content assay platform for mechanistic studies and drug discovery. Here, we explored the spontaneous and evoked electrical activity of VH cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs. Primary VH cultures from embryonic day 15-16 mice were characterized by expression of choline acetyltransferase (ChAT) by immunocytochemistry...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29030733/high-yield-preparation-of-functionally-active-catalytic-translocation-domain-module-of-botulinum-neurotoxin-type-a-that-exhibits-uniquely-different-enzyme-kinetics
#3
Harkiranpreet Kaur Dhaliwal, Nagarajan Thiruvanakarasu, Raj Kumar, Kruti Patel, Ghuncha Ambrin, Shouwei Cai, Bal Ram Singh
Botulinum neurotoxins (BoNTs) are the most toxic proteins known to cause flaccid muscle paralysis as a result of inhibition of neurotransmitter release from peripheral cholinergic synapses. BoNT type A (BoNT/A) is a 150 kDa protein consisting of two major subunits: light chain (LC) and heavy chain (HC). The LC is required for the catalytic activity of neurotoxin, whereas the C and N terminal domains of the HC are required for cell binding, and translocation of LC across the endosome membranes, respectively...
October 13, 2017: Protein Journal
https://www.readbyqxmd.com/read/28982136/augmentation-of-vamp-catalytic-activity-of-botulinum-neurotoxin-serotype-b-does-not-result-in-increased-potency-in-physiological-systems
#4
Mark Elliott, Jacquie Maignel, Sai Man Liu, Christine Favre-Guilmard, Imran Mir, Paul Farrow, Fraser Hornby, Sandra Marlin, Shilpa Palan, Matthew Beard, Johannes Krupp
Botulinum neurotoxins (BoNTs) are used extensively as therapeutic agents. Serotypes A and B are available as marketed products. Higher doses of BoNT/B are required to reach an efficacy similar to that of products containing BoNT/A. Advances in our understanding of BoNT/B mechanism of action have afforded the opportunity to make rational modifications to the toxin aimed at increasing its activity. Recently, a mutation in the light chain of BoNT/B (S201P) was described that increases the catalytic activity of the isolated BoNT/B light chain in biochemical assays...
2017: PloS One
https://www.readbyqxmd.com/read/28918229/design-of-modified-botulinum-neurotoxin-a1-variants-with-a-shorter-persistence-of-paralysis-and-duration-of-action
#5
Daniel Scheps, Manuela López de la Paz, Marcel Jurk, Fred Hofmann, Jürgen Frevert
Botulinum neurotoxins (BoNTs) are classified by their antigenic properties into seven serotypes (A-G) and in addition by their corresponding subtypes. They are further characterized by divergent onset and duration of effect. Injections of low doses of botulinum neurotoxins cause localized muscle paralysis that is beneficial for the treatment of several medical disorders and aesthetic indications. Optimizing the therapeutic properties could offer new treatment opportunities. This report describes a rational design approach to modify the pharmacological properties by mutations in the C-terminus of BoNT/A1 light chain (LC)...
September 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28898517/characterization-of-the-functional-activity-of-botulinum-neurotoxin-subtype-b6
#6
Tomoko Kohda, Keiji Nakamura, Koji Hosomi, Yasushi Torii, Shunji Kozaki, Masafumi Mukamoto
Clostridium botulinum produces the highly potent neurotoxin, botulinum neurotoxin (BoNT), which is classified into seven serotypes, A-G, and the subtype classification is confirmed by the diversity of the amino acid sequence among the serotypes. The BoNT from the Osaka05 strain is associated with type B infant botulism and has been divided into BoNT/B subtype B6 (BoNT/B6) by phylogenetic analysis and the antigenicity of its C-terminal heavy chain (HC) domain. However, the molecular basis for its properties, including the potency, is poorly understood...
September 12, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28891721/the-regions-on-the-light-chain-of-botulinum-neurotoxin-type-a-recognized-by-t-cells-from-toxin-treated-cervical-dystonia-patients-the-complete-human-t-cell-recognition-map-of-the-toxin-molecule
#7
Minako Oshima, Philip Deitiker, Joseph Jankovic, M Zouhair Atassi
We have recently mapped the in vitro proliferative responses of T cells from botulinum neurotoxin type A (BoNT/A)-treated cervical dystonia (CD) patients with overlapping peptides encompassing BoNT/A heavy chain (residues 449-1296). In the present study, we determined the recognition profiles, by peripheral blood lymphocytes (PBL) from the same set of patients, of BoNT/A light (L) chain (residues 1-453) by using 32 synthetic overlapping peptides that encompassed the entire L chain. Profiles of the T-cell responses (expressed in stimulation index, SI; Z score based on transformed SI) to the peptides varied among the patients...
September 11, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28879524/uptake-of-clostridial-neurotoxins-into-cells-and-dissemination
#8
Chloé Connan, Michel R Popoff
Clostridial neurotoxins, botulinum neurotoxins (BoNT) and tetanus neurotoxin (TeNT), are potent toxins, which are responsible for severe neurological diseases in man and animals. BoNTs induce a flaccid paralysis (botulism) by inhibiting acetylcholine release at the neuromuscular junctions, whereas TeNT causes a spastic paralysis (tetanus) by blocking the neurotransmitter release (glycine, GABA) in inhibitory interneurons within the central nervous system. Clostridial neurotoxins recognize specific receptor(s) on the target neuronal cells and enter via a receptor-mediated endocytosis...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28843941/botulinum-neurotoxin-and-its-potential-role-in-the-treatment-of-erectile-dysfunction
#9
REVIEW
Hussein Ghanem, Amr Abdel Raheem, Islam Fathy Soliman AbdelRahman, Mark Johnson, Tarek Abdel-Raheem
INTRODUCTION: Botulinum toxin type A (BoNT-A) has been used to treat several striated and smooth muscle disorders. During the past year, human and animal studies conducted in Egypt and Canada by two different groups of investigators have suggested a possible role for the intracavernosal injection of BoNT-A in the treatment of erectile dysfunction (ED). AIM: To discuss BoNT-A and its current medical uses, the rationale for its new potential use in the treatment of ED, and the available evidence and concerns...
August 23, 2017: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/28840969/intraprostatic-botulinum-toxin-type-a-injection-in-patients-with-benign-prostatic-hyperplasia-and-unsatisfactory-response-to-medical-therapy-a-randomized-double-blind-controlled-trial-using-urodynamic-evaluation
#10
Angelo Totaro, Francesco Pinto, Dario Pugliese, Matteo Vittori, Marco Racioppi, Nazario Foschi, Pier Francesco Bassi, Emilio Sacco
AIMS: The injection of botulinum neurotoxin A (BTA) into the prostate represents a minimally invasive treatment in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). We evaluated the effectiveness of BTA in treating patients with BPH unresponsive to combined medical therapy (CMT), using urodynamic investigations. METHODS: This is a randomized, placebo-controlled, double blind trial. Twenty consecutive patients were randomly assigned to receive intraprostatic BTA injection (n = 10) or saline solution (SS) (n = 10)...
August 25, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28816652/reoccurrence-of-botulinum-neurotoxin-subtype-a3-inducing-food-borne-botulism-slovakia-2015
#11
Lucia Mad'arová, Brigitte G Dorner, Lars Schaade, Vladimír Donáth, Mária Avdičová, Milota Fatkulinová, Jozef Strhársky, Ivana Sedliačiková, Cyril Klement, Martin B Dorner
A case of food-borne botulism occurred in Slovakia in 2015. Clostridium botulinum type A was isolated from three nearly empty commercial hummus tubes. The product, which was sold in Slovakia and the Czech Republic, was withdrawn from the market and a warning was issued immediately through the European Commission's Rapid Alert System for Food and Feed (RASFF). Further investigation revealed the presence of botulinum neurotoxin (BoNT) subtype BoNT/A3, a very rare subtype implicated in only one previous outbreak (Loch Maree in Scotland, 1922)...
August 10, 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/28809452/neurotoxin-synthesis-is-positively-regulated-by-the-sporulation-transcription-factor-spo0a-in-clostridium-botulinum-type-e
#12
Gerald Mascher, Anna Mertaoja, Hannu Korkeala, Miia Lindström
Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C. botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C. botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild-type controls...
August 15, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28802703/identification-and-characterization-of-clostridium-botulinum-group-iii-field-strains-by-matrix-assisted-laser-desorption-ionization-time-of-flight-mass-spectrometry-maldi-tof-ms
#13
Luca Bano, Ilenia Drigo, Elena Tonon, Simone Pascoletti, Cinzia Puiatti, Fabrizio Anniballi, Bruna Auricchio, Florigio Lista, Cesare Montecucco, Fabrizio Agnoletti
Animal botulism is primarily due to botulinum neurotoxin (BoNT) types C, D or their chimeric variants C/D or D/C, produced by Clostridium botulinum group III, which appears to include the genetically indistinguishable Clostridium haemolyticum and Clostridium novyi. In the present study, we used matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI TOF MS) to identify and characterize 81 BoNT-producing Clostridia isolated in 47 episodes of animal botulism. The instrument's default database, containing no entries for Clostridium botulinum, permitted reliable identification of 26 strains at the genus level...
August 10, 2017: Anaerobe
https://www.readbyqxmd.com/read/28800600/botulinum-neurotoxin-c-mutants-reveal-different-effects-of-syntaxin-or-snap-25-proteolysis-on-neuromuscular-transmission
#14
Giulia Zanetti, Stefan Sikorra, Andreas Rummel, Nadja Krez, Elisa Duregotti, Samuele Negro, Tina Henke, Ornella Rossetto, Thomas Binz, Marco Pirazzini
Botulinum neurotoxin serotype C (BoNT/C) is a neuroparalytic toxin associated with outbreaks of animal botulism, particularly in birds, and is the only BoNT known to cleave two different SNARE proteins, SNAP-25 and syntaxin. BoNT/C was shown to be a good substitute for BoNT/A1 in human dystonia therapy because of its long lasting effects and absence of neuromuscular damage. Two triple mutants of BoNT/C, namely BoNT/C S51T/R52N/N53P (BoNT/C α-51) and BoNT/C L200W/M221W/I226W (BoNT/C α-3W), were recently reported to selectively cleave syntaxin and have been used here to evaluate the individual contribution of SNAP-25 and syntaxin cleavage to the effect of BoNT/C in vivo...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28800585/comparative-pathogenomics-of-clostridium-tetani
#15
COMPARATIVE STUDY
Jonathan E Cohen, Rong Wang, Rong-Fong Shen, Wells W Wu, James E Keller
Clostridium tetani and Clostridium botulinum produce two of the most potent neurotoxins known, tetanus neurotoxin and botulinum neurotoxin, respectively. Extensive biochemical and genetic investigation has been devoted to identifying and characterizing various C. botulinum strains. Less effort has been focused on studying C. tetani likely because recently sequenced strains of C. tetani show much less genetic diversity than C. botulinum strains and because widespread vaccination efforts have reduced the public health threat from tetanus...
2017: PloS One
https://www.readbyqxmd.com/read/28783115/a-novel-surface-plasmon-resonance-biosensor-for-the-rapid-detection-of-botulinum-neurotoxins
#16
Kruti Patel, Shmuel Halevi, Paul Melman, John Schwartz, Shuowei Cai, Bal Ram Singh
Botulinum neurotoxins (BoNTs) are Category A agents on the NIAID (National Institute of Allergy and Infectious Diseases) priority pathogen list owing to their extreme toxicity and the relative ease of production. These deadly toxins, in minute quantities (estimated human i.v. lethal dose LD50 of 1-2 ng/kg body weight), cause fatal flaccid paralysis by blocking neurotransmitter release. The current gold standard detection method, the mouse-bioassay, often takes days to confirm botulism. Furthermore, there are no effective antidotes known to reverse the symptoms of botulism, and as a result, patients with severe botulism often require meticulous care during the prolonged paralytic illness...
August 7, 2017: Biosensors
https://www.readbyqxmd.com/read/28770389/long-term-stability-of-reconstituted-incobotulinumtoxina-how-can-we-reduce-costs-of-botulinum-toxin-therapy
#17
Dirk Dressler, Hans Bigalke
Botulinum neurotoxin (BNT), the biologically active component of botulinum toxin (BT), is a large double-stranded protein susceptible to various physical and chemical influences. All BT type A (BT-A) drugs are stored as powders allowing shelf lives from 24 to 36 months. After reconstitution, the specified shelf life is reduced to 8-24 h. Some studies, however, suggest longer shelf life. We wanted to test the long-term stability of reconstituted BT-A drugs in the hemidiaphragm assay (HDA), a high quality BT potency test...
August 2, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28733282/differentiating-botulinum-neurotoxin-producing-clostridia-with-a-simple-multiplex-pcr-assay
#18
Charles H D Williamson, Adam J Vazquez, Karen Hill, Theresa J Smith, Roxanne Nottingham, Nathan E Stone, Colin J Sobek, Jill H Cocking, Rafael A Fernández, Patricia A Caballero, Owen P Leiser, Paul Keim, Jason W Sahl
Diverse members of the genus Clostridium produce botulinum neurotoxins (BoNTs), which cause a flaccid paralysis known as botulism. While multiple species of clostridia produce BoNTs, the majority of human botulism cases have been attributed to Clostridium botulinum groups I and II. Recent comparative genomic studies have demonstrated the genomic diversity within these BoNT-producing species. This report introduces a multiplex PCR assay for differentiating members of C. botulinum group I, C. sporogenes, and two major subgroups within C...
September 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28727388/lysozyme-gene-treatment-in-testosterone-induced-benign-prostate-hyperplasia-rat-model-and-comparasion-of-its-effectiveness-with-botulinum-toxin-injection
#19
Osman Ergün, Pinar Aslan Koşar, İbrahim Onaran, Hakan Darici, Alim Koşar
OBJECTIVES: To compare the effects and histopathological changes of botulinum neurotoxin type A and lysozyme gene injections into prostate tissue within a testosterone induced benign prostate hyperplasia rat model. MATERIALS AND METHODS: 40 male Wistar rats were randomized into four Groups. Group-1: Control, Group-2: Testosterone replacement, Group-3: Testosterone+botulinum neurotoxin type A, Group-4: Testosterone+plazmid DNA/liposome complex. RESULTS: Estimated prostate volume of the testosterone injected Groups were higher than the control (p <0...
July 20, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28705271/molecular-and-epidemiological-characterization-of-infant-botulism-in-beijing-china
#20
Yin Ping Dong, Wei Wang, Tao Jiang, Jin Xu, Chun Hui Han, Shao Fei Yan, Séamus Fanning, Ying Li, Xiao Chen Ma, Di Zhang, Yao Zhao, Biao Zeng, Feng Qin Li
Laboratory-based pathogen isolation, identification, and toxicity determination were performed on samples from a suspected case of infant botulism. Mice injected with cultures generated from the enema sample and ingested Powered infant formula (PIF) presented typical signs of botulism. Antitoxins to polyvalent botulinum neurotoxins (BoNTs) and monovalent BoNT type B antitoxin had protective effects. Clostridium botulinum isolated from the enema and residual PIF samples were positive for type B toxin. Pulsed-field gel electrophoresis (PFGE) revealed that the two strains of C...
June 2017: Biomedical and Environmental Sciences: BES
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