Biological Toxins As the Potential Tools for Bioterrorism
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The Food Poisoning Toxins of Bacillus Cereus
toxins Review The Food Poisoning Toxins of Bacillus cereus Richard Dietrich 1,†, Nadja Jessberger 1,*,†, Monika Ehling-Schulz 2 , Erwin Märtlbauer 1 and Per Einar Granum 3 1 Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig Maximilian University of Munich, Schönleutnerstr. 8, 85764 Oberschleißheim, Germany; [email protected] (R.D.); [email protected] (E.M.) 2 Department of Pathobiology, Functional Microbiology, Institute of Microbiology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria; [email protected] 3 Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003 NMBU, 1432 Ås, Norway; [email protected] * Correspondence: [email protected] † These authors have contributed equally to this work. Abstract: Bacillus cereus is a ubiquitous soil bacterium responsible for two types of food-associated gastrointestinal diseases. While the emetic type, a food intoxication, manifests in nausea and vomiting, food infections with enteropathogenic strains cause diarrhea and abdominal pain. Causative toxins are the cyclic dodecadepsipeptide cereulide, and the proteinaceous enterotoxins hemolysin BL (Hbl), nonhemolytic enterotoxin (Nhe) and cytotoxin K (CytK), respectively. This review covers the current knowledge on distribution and genetic organization of the toxin genes, as well as mechanisms of enterotoxin gene regulation and toxin secretion. In this context, the exceptionally high variability of toxin production between single strains is highlighted. In addition, the mode of action of the pore-forming enterotoxins and their effect on target cells is described in detail. The main focus of this review are the two tripartite enterotoxin complexes Hbl and Nhe, but the latest findings on cereulide and CytK are also presented, as well as methods for toxin detection, and the contribution of further putative virulence factors to the diarrheal disease. -
Rapid and Simultaneous Detection of Ricin, Staphylococcal Enterotoxin B
Analyst PAPER View Article Online View Journal | View Issue Rapid and simultaneous detection of ricin, staphylococcal enterotoxin B and saxitoxin by Cite this: Analyst,2014,139, 5885 chemiluminescence-based microarray immunoassay† a a b b c c A. Szkola, E. M. Linares, S. Worbs, B. G. Dorner, R. Dietrich, E. Martlbauer,¨ R. Niessnera and M. Seidel*a Simultaneous detection of small and large molecules on microarray immunoassays is a challenge that limits some applications in multiplex analysis. This is the case for biosecurity, where fast, cheap and reliable simultaneous detection of proteotoxins and small toxins is needed. Two highly relevant proteotoxins, ricin (60 kDa) and bacterial toxin staphylococcal enterotoxin B (SEB, 30 kDa) and the small phycotoxin saxitoxin (STX, 0.3 kDa) are potential biological warfare agents and require an analytical tool for simultaneous detection. Proteotoxins are successfully detected by sandwich immunoassays, whereas Creative Commons Attribution-NonCommercial 3.0 Unported Licence. competitive immunoassays are more suitable for small toxins (<1 kDa). Based on this need, this work provides a novel and efficient solution based on anti-idiotypic antibodies for small molecules to combine both assay principles on one microarray. The biotoxin measurements are performed on a flow-through chemiluminescence microarray platform MCR3 in 18 minutes. The chemiluminescence signal was Received 18th February 2014 amplified by using a poly-horseradish peroxidase complex (polyHRP), resulting in low detection limits: Accepted 3rd September 2014 2.9 Æ 3.1 mgLÀ1 for ricin, 0.1 Æ 0.1 mgLÀ1 for SEB and 2.3 Æ 1.7 mgLÀ1 for STX. The developed multiplex DOI: 10.1039/c4an00345d system for the three biotoxins is completely novel, relevant in the context of biosecurity and establishes www.rsc.org/analyst the basis for research on anti-idiotypic antibodies for microarray immunoassays. -
Pandemic Disease, Biological Weapons, and War
Georgetown University Law Center Scholarship @ GEORGETOWN LAW 2014 Pandemic Disease, Biological Weapons, and War Laura K. Donohue Georgetown University Law Center, [email protected] This paper can be downloaded free of charge from: https://scholarship.law.georgetown.edu/facpub/1296 http://ssrn.com/abstract=2350304 Laura K. Donohue, Pandemic Disease, Biological Weapons, and War in LAW AND WAR: (Sarat, Austin, Douglas, Lawrence, and Umphrey, Martha Merrill, eds., Stanford University Press, 2014) This open-access article is brought to you by the Georgetown Law Library. Posted with permission of the author. Follow this and additional works at: https://scholarship.law.georgetown.edu/facpub Part of the Defense and Security Studies Commons, Military and Veterans Studies Commons, Military, War, and Peace Commons, and the National Security Law Commons PANDEMIC DISEASE , BIOLOGICAL WEAPONS , AND WAR Laura K. Donohue * Over the past two decades, concern about the threat posed by biological weapons has grown. Biowarfare is not new. 1 But prior to the recent trend, the threat largely centered on state use of such weapons. 2 What changed with the end of the Cold War was the growing apprehension that materials and knowledge would proliferate beyond industrialized states’ control, and that “rogue states” or nonstate actors would acquire and use biological weapons. 3 Accordingly, in 1993 senators Samuel Nunn, Richard Lugar, and Pete Dominici expanded the Cooperative Threat Reduction Program to assist the former Soviet republics in securing biological agents and weapons knowledge. The Defense Against Weapons of Mass Destruction Act gave the Pentagon lead agency responsibility. 4 Senator Lugar explained, “[B]iological weapons, materials, and know-how are now more available to terrorists and rogue nations than at any other time in our history.”5 The United States was not equipped to manage the crisis. -
Detoxification Strategies for Zearalenone Using
microorganisms Review Detoxification Strategies for Zearalenone Using Microorganisms: A Review 1, 2, 1 1, Nan Wang y, Weiwei Wu y, Jiawen Pan and Miao Long * 1 Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China 2 Institute of Animal Science, Xinjiang Academy of Animal Sciences, Urumqi 830000, China * Correspondence: [email protected] or [email protected] These authors contributed equally to this work. y Received: 21 June 2019; Accepted: 19 July 2019; Published: 21 July 2019 Abstract: Zearalenone (ZEA) is a mycotoxin produced by Fusarium fungi that is commonly found in cereal crops. ZEA has an estrogen-like effect which affects the reproductive function of animals. It also damages the liver and kidneys and reduces immune function which leads to cytotoxicity and immunotoxicity. At present, the detoxification of mycotoxins is mainly accomplished using biological methods. Microbial-based methods involve zearalenone conversion or adsorption, but not all transformation products are nontoxic. In this paper, the non-pathogenic microorganisms which have been found to detoxify ZEA in recent years are summarized. Then, two mechanisms by which ZEA can be detoxified (adsorption and biotransformation) are discussed in more detail. The compounds produced by the subsequent degradation of ZEA and the heterogeneous expression of ZEA-degrading enzymes are also analyzed. The development trends in the use of probiotics as a ZEA detoxification strategy are also evaluated. The overall purpose of this paper is to provide a reliable reference strategy for the biological detoxification of ZEA. Keywords: zearalenone (ZEA); reproductive toxicity; cytotoxicity; immunotoxicity; biological detoxification; probiotics; ZEA biotransformation 1. -
The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections
toxins Review The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections Patience Shumba 1, Srikanth Mairpady Shambat 2 and Nikolai Siemens 1,* 1 Center for Functional Genomics of Microbes, Department of Molecular Genetics and Infection Biology, University of Greifswald, D-17489 Greifswald, Germany; [email protected] 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland; [email protected] * Correspondence: [email protected]; Tel.: +49-3834-420-5711 Received: 20 May 2019; Accepted: 10 June 2019; Published: 11 June 2019 Abstract: Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies. Keywords: Streptococcus pyogenes; group A streptococcus; Staphylococcus aureus; skin infections; necrotizing soft tissue infections; pore-forming toxins; superantigens; immunomodulatory proteases; immune responses Key Contribution: Group A streptococcal and Staphylococcus aureus toxins manipulate host physiological and immunological responses to promote disease severity and progression. 1. Introduction Necrotizing soft tissue infections (NSTIs) are rare and represent a more severe rapidly progressing form of soft tissue infections that account for significant morbidity and mortality [1]. -
Clostridium Perfringens Enterotoxin: the Toxin Forms Highly Cation-Selective Channels in Lipid Bilayers Roland Benz, Michel Popoff
Clostridium perfringens Enterotoxin: The Toxin Forms Highly Cation-Selective Channels in Lipid Bilayers Roland Benz, Michel Popoff To cite this version: Roland Benz, Michel Popoff. Clostridium perfringens Enterotoxin: The Toxin Forms Highly Cation- Selective Channels in Lipid Bilayers. Toxins, MDPI, 2018, 10 (9), pp.341. 10.3390/toxins10090341. pasteur-02448636 HAL Id: pasteur-02448636 https://hal-pasteur.archives-ouvertes.fr/pasteur-02448636 Submitted on 22 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License toxins Article Clostridium perfringens Enterotoxin: The Toxin Forms Highly Cation-Selective Channels in Lipid Bilayers Roland Benz 1 ID and Michel R. Popoff 2,* 1 Department of Life Sciences and Chemistry, Jacobs University, Campusring 1, 28759 Bremen, Germany; [email protected] 2 Bacterial Toxins, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France * Correspondence: [email protected] Received: 30 July 2018; Accepted: 14 August 2018; Published: 22 August 2018 Abstract: One of the numerous toxins produced by Clostridium perfringens is Clostridium perfringens enterotoxin (CPE), a polypeptide with a molecular mass of 35.5 kDa exhibiting three different domains. -
Interactions of Insecticidal Spider Peptide Neurotoxins with Insect Voltage- and Neurotransmitter-Gated Ion Channels
Interactions of insecticidal spider peptide neurotoxins with insect voltage- and neurotransmitter-gated ion channels (Molecular representation of - HXTX-Hv1c including key binding residues, adapted from Gunning et al, 2008) PhD Thesis Monique J. Windley UTS 2012 CERTIFICATE OF AUTHORSHIP/ORIGINALITY I certify that the work in this thesis has not previously been submitted for a degree nor has it been submitted as part of requirements for a degree except as fully acknowledged within the text. I also certify that the thesis has been written by me. Any help that I have received in my research work and the preparation of the thesis itself has been acknowledged. In addition, I certify that all information sources and literature used are indicated in the thesis. Monique J. Windley 2012 ii ACKNOWLEDGEMENTS There are many people who I would like to thank for contributions made towards the completion of this thesis. Firstly, I would like to thank my supervisor Prof. Graham Nicholson for his guidance and persistence throughout this project. I would like to acknowledge his invaluable advice, encouragement and his neverending determination to find a solution to any problem. He has been a valuable mentor and has contributed immensely to the success of this project. Next I would like to thank everyone at UTS who assisted in the advancement of this research. Firstly, I would like to acknowledge Phil Laurance for his assistance in the repair and modification of laboratory equipment. To all the laboratory and technical staff, particulary Harry Simpson and Stan Yiu for the restoration and sourcing of equipment - thankyou. I would like to thank Dr Mike Johnson for his continual assistance, advice and cheerful disposition. -
OECD Guidance Document Number 24: Acute Oral Toxicity Testing
Unclassified ENV/JM/MONO(2001)4 Organisation de Coopération et de Développement Economiques Organisation for Economic Co-operation and Development 23-Jul-2001 ___________________________________________________________________________________________ English - Or. English ENVIRONMENT DIRECTORATE Unclassified ENV/JM/MONO(2001)4 JOINT MEETING OF THE CHEMICALS COMMITTEE AND THE WORKING PARTY ON CHEMICALS, PESTICIDES AND BIOTECHNOLOGY OECD SERIES ON TESTING AND ASSESSMENT Number 24 GUIDANCE DOCUMENT ON ACUTE ORAL TOXICITY TESTING English - Or. English JT00111082 Document complet disponible sur OLIS dans son format d’origine Complete document available on OLIS in its original format ENV/JM/MONO(2001)4 2 ENV/JM/MONO(2001)4 OECD Environment, Health and Safety Publications Series on Testing and Assessment No 24 GUIDANCE DOCUMENT ON ACUTE ORAL TOXICITY TESTING Environment Directorate ORGANISATION FOR ECONOMIC CO-OPERATION AND DEVELOPMENT Paris June 2001 3 ENV/JM/MONO(2001)4 Also published in the Series on Testing and Assessment No. 1, Guidance Document for the Development of OECD Guidelines for Testing of Chemicals (1993; reformatted 1995) No. 2, Detailed Review Paper on Biodegradability Testing (1995) No. 3, Guidance Document for Aquatic Effects Assessment (1995) No. 4, Report of the OECD Workshop on Environmental Hazard/Risk Assessment (1995) No. 5, Report of the SETAC/OECD Workshop on Avian Toxicity Testing (1996) No. 6, Report of the Final Ring-test of the Daphnia magna Reproduction Test (1997) No. 7, Guidance Document on Direct Phototransformation of Chemicals in Water (1997) No. 8, Report of the OECD Workshop on Sharing Information about New Industrial Chemicals Assessment (1997) No. 9, Guidance Document for the Conduct of Studies of Occupational Exposure to Pesticides During Agricultural Application (1997) No. -
In Defense of Cyberterrorism: an Argument for Anticipating Cyber-Attacks
IN DEFENSE OF CYBERTERRORISM: AN ARGUMENT FOR ANTICIPATING CYBER-ATTACKS Susan W. Brenner Marc D. Goodman The September 11, 2001, terrorist attacks on the United States brought the notion of terrorism as a clear and present danger into the consciousness of the American people. In order to predict what might follow these shocking attacks, it is necessary to examine the ideologies and motives of their perpetrators, and the methodologies that terrorists utilize. The focus of this article is on how Al-Qa'ida and other Islamic fundamentalist groups can use cyberspace and technology to continue to wage war againstthe United States, its allies and its foreign interests. Contending that cyberspace will become an increasingly essential terrorist tool, the author examines four key issues surrounding cyberterrorism. The first is a survey of conventional methods of "physical" terrorism, and their inherent shortcomings. Next, a discussion of cyberspace reveals its potential advantages as a secure, borderless, anonymous, and structured delivery method for terrorism. Third, the author offers several cyberterrorism scenarios. Relating several examples of both actual and potential syntactic and semantic attacks, instigated individually or in combination, the author conveys their damagingpolitical and economic impact. Finally, the author addresses the inevitable inquiry into why cyberspace has not been used to its full potential by would-be terrorists. Separately considering foreign and domestic terrorists, it becomes evident that the aims of terrorists must shift from the gross infliction of panic, death and destruction to the crippling of key information systems before cyberattacks will take precedence over physical attacks. However, given that terrorist groups such as Al Qa'ida are highly intelligent, well-funded, and globally coordinated, the possibility of attacks via cyberspace should make America increasingly vigilant. -
Mycotoxins: a Review of Dairy Concerns
Mycotoxins: A Review of Dairy Concerns L. W. Whitlow, Department of Animal Science and W. M. Hagler, Jr., Department of Poultry Science North Carolina State University, Raleigh, NC 27695 Introduction mycotoxins such as the ergots are known to affect cattle and may be prevalent at times in certain feedstuffs. Molds are filamentous (fuzzy or dusty looking) fungi that occur in many feedstuffs including roughages and There are hundreds of different mycotoxins, which are concentrates. Molds can infect dairy cattle, especially diverse in their chemistry and effects on animals. It is during stressful periods when they are immune likely that contaminated feeds will contain more than one suppressed, causing a disease referred to as mycosis. mycotoxin. This paper is directed toward those Molds also produce poisons called mycotoxins that affect mycotoxins thought to occur most frequently at animals when they consume mycotoxin contaminated concentrations toxic to dairy cattle. A more extensive feeds. This disorder is called mycotoxicosis. Mycotoxins review is available in the popular press (Whitlow and are produced by a wide range of different molds and are Hagler, 2004). classified as secondary metabolites, meaning that their function is not essential to the mold’s existence. The Major toxigenic fungi and mycotoxins thought to be U.N.’s Food and Agriculture Organization (FAO) has the most prevalent and potentially toxic to dairy cattle. estimated that worldwide, about 25% of crops are affected annually with mycotoxins (Jelinek, 1987). Such surveys Fungal genera Mycotoxins reveal sufficiently high occurrences and concentrations of Aspergillus Aflatoxin, Ochratoxin, mycotoxins to suggest that mycotoxins are a constant Sterigmatocystin, Fumitremorgens, concern. -
Biological Toxins Fact Sheet
Work with FACT SHEET Biological Toxins The University of Utah Institutional Biosafety Committee (IBC) reviews registrations for work with, possession of, use of, and transfer of acute biological toxins (mammalian LD50 <100 µg/kg body weight) or toxins that fall under the Federal Select Agent Guidelines, as well as the organisms, both natural and recombinant, which produce these toxins Toxins Requiring IBC Registration Laboratory Practices Guidelines for working with biological toxins can be found The following toxins require registration with the IBC. The list in Appendix I of the Biosafety in Microbiological and is not comprehensive. Any toxin with an LD50 greater than 100 µg/kg body weight, or on the select agent list requires Biomedical Laboratories registration. Principal investigators should confirm whether or (http://www.cdc.gov/biosafety/publications/bmbl5/i not the toxins they propose to work with require IBC ndex.htm). These are summarized below. registration by contacting the OEHS Biosafety Officer at [email protected] or 801-581-6590. Routine operations with dilute toxin solutions are Abrin conducted using Biosafety Level 2 (BSL2) practices and Aflatoxin these must be detailed in the IBC protocol and will be Bacillus anthracis edema factor verified during the inspection by OEHS staff prior to IBC Bacillus anthracis lethal toxin Botulinum neurotoxins approval. BSL2 Inspection checklists can be found here Brevetoxin (http://oehs.utah.edu/research-safety/biosafety/ Cholera toxin biosafety-laboratory-audits). All personnel working with Clostridium difficile toxin biological toxins or accessing a toxin laboratory must be Clostridium perfringens toxins Conotoxins trained in the theory and practice of the toxins to be used, Dendrotoxin (DTX) with special emphasis on the nature of the hazards Diacetoxyscirpenol (DAS) associated with laboratory operations and should be Diphtheria toxin familiar with the signs and symptoms of toxin exposure. -
China's False Allegations of the Use of Biological Weapons by the United
W O R K I N G P A P E R # 7 8 China’s False Allegations of the Use of Biological Weapons by the United States during the Korean War By Milton Leitenberg, March 2016 THE COLD WAR INTERNATIONAL HISTORY PROJECT WORKING PAPER SERIES Christian F. Ostermann, Series Editor This paper is one of a series of Working Papers published by the Cold War International History Project of the Woodrow Wilson International Center for Scholars in Washington, D.C. Established in 1991 by a grant from the John D. and Catherine T. MacArthur Foundation, the Cold War International History Project (CWIHP) disseminates new information and perspectives on the history of the Cold War as it emerges from previously inaccessible sources on “the other side” of the post-World War II superpower rivalry. The project supports the full and prompt release of historical materials by governments on all sides of the Cold War, and seeks to accelerate the process of integrating new sources, materials and perspectives from the former “Communist bloc” with the historiography of the Cold War which has been written over the past few decades largely by Western scholars reliant on Western archival sources. It also seeks to transcend barriers of language, geography, and regional specialization to create new links among scholars interested in Cold War history. Among the activities undertaken by the project to promote this aim are a periodic BULLETIN to disseminate new findings, views, and activities pertaining to Cold War history; a fellowship program for young historians from the former Communist bloc to conduct archival research and study Cold War history in the United States; international scholarly meetings, conferences, and seminars; and publications.