Exotoxins

9 Key excerpts on "Exotoxins"

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  eBook - ePub

  Bacterial Pathogenesis

  A Molecular Approach

  • Brenda A. Wilson, Malcolm Winkler, Brian T. Ho, Brenda A. Wilson, Malcolm Winkler(Authors)
  • 2019(Publication Date)
  • ASM Press

    (Publisher)

  A term that has sometimes been used to designate the protein toxins of bacteria is exotoxin. The word “exotoxin” was chosen to emphasize the fact that the toxins are secreted from the cell into the medium, in contrast to endotoxins, which are components of the bacterial surface and mainly get released through bacterial cell lysis. The term “exotoxin” has been falling out of use because some protein toxins are not secreted but rather accumulate inside the bacterial cell and are released by cell lysis. Others are injected directly into human or animal cells, thereby bypassing the extracellular environment entirely. These toxins are often referred to as effector proteins or exoenzymes and are directly delivered into the host cell via specialized secretion systems. We will cover secretion systems and delivery of virulence factors in more detail later in chapter 13. For convenience, we will use the word “toxin” to mean all types of virulence factors of bacteria, whether secreted or not, that are toxic to the human or animal host. Bacterial toxins vary considerably not only in their structures and activities, but also in the host cell types they attack. Names given to different toxins reflect this diversity. Some toxins are simply given letter designations (e.g., exotoxin A of Pseudomonas aeruginosa), while other toxins are named for the numerical, Greek, Roman, or alphabetical order in which they were isolated or discovered from a bacterial species, such as the alpha-, beta-, gamma-, delta-, and epsilon-toxins produced by Clostridium perfringens. Some toxins are named to indicate what type of host cells they attack

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  Food Microbiology

  Principles into Practice

  • Osman Erkmen, T. Faruk Bozoglu(Authors)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  Exotoxin is the term used to describe toxins that are released extracellularly by living bacteria during exponential growth. In some cases, Exotoxins can also be released by lysis of the bacterial cell or may be removed from the side of bacterial growth. Exotoxins are usually proteins, minimally polypeptides that act enzymatically or through direct action with host cells and stimulate a variety of host responses. Bacterial Exotoxins act at the site of pathogen colonization and growth, and some bacterial toxins promote bacterial invasion. Exotoxins have toxicity and antigenicity. These include enterotoxins that act on the intestinal mucosa and generally cause diarrhea, cytotoxins that kill host cells, and neurotoxins that interfere with normal nervous transmission. Several bacterial Exotoxins can act directly in the immune system and can cause impairment to the immunologic functions. These toxins are called pyrogenic Exotoxins produced by staphylococci (enterotoxins) and streptococci (pyrogenic Exotoxins).

  Exotoxins of bacteria have different pathogenic ability. C. tetani exotoxin blocks action of neurons of spinal cord and causes tetanus. C. perfringens exotoxin (enterotoxin) causes gas gangrene. Exotoxin (alpha toxin) has lecithinase activity and thereby causes cell death. Its enterotoxin causes secretion of water and electrolytes in diarrhea. Clostridium botulinum exotoxin (neurotoxin) causes paralysis respiratory muscles, and blocks release of acetylcholine of synapses and neuromuscular junctions. V. cholerae (strains 01 and 0139) exotoxin (enterotoxin) causes secretion of water and electrolytes within the gut in diarrhea. Enterotoxigenic E. coli exotoxin (heat labile exotoxin) causes secretion of water and electrolytes within the gut. S. dysenteriae exotoxin causes acute inflammation. S. aureus exotoxin (enterotoxin) causes toxic shock syndrome, stimulates vomiting center of brain, and associates with watery diarrhea. S. pyogenes exotoxin (erythrogenic toxin) causes scarlet fever and toxic shock syndrome. Some other pathogenic bacteria producing Exotoxins (enterotoxins) are Vibrio parahaemolyticus, Yersinia enterocolitica, and Aeromonas hydrophilia

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  Concepts in Bacterial Virulence

  • W. Russell, H. Herwald, A. Schmidt, H. Herwald(Authors)
  • 2004(Publication Date)
  • S. Karger

    (Publisher)

  New York, Plenum Press, 1995, pp 495–524. Russell E. Bishop 6213 Medical Sciences Building, 1 King’s College Circle Toronto, Ont. M5S 1A8 (Canada) Tel. 1 416 946 7103, Fax 1 416 978 5959, E-Mail [email protected] Russell W, Herwald H (eds): Concepts in Bacterial Virulence. Contrib Microbiol. Basel, Karger, 2004, vol 12, pp 28–54 Bacterial Exotoxins Michel R. Popoff Unité des Bactéries anaérobies et Toxines, Institut Pasteur, Paris, France Amongst the various mechanisms developed by pathogenic bacteria to cause disease, toxins play an important role, since they are responsible for the majority of symptoms and lesions during infection. Exotoxins act at a distance from the infectious site and can diffuse through the organism. While some cytotoxins can cause disruption of cells permitting the pathogens access to nutri-ents, other toxins are only active on specific cells, for example intestinal cells, neuronal cells, or leukocytes. This is achieved by the recognition of specific cell surface receptors. When bound to the receptor, toxins can unleash their toxic program at the cell membrane by interfering with signal transduction pathways, pore formation, or enzymatic activities towards membrane compounds. In con-trast, other toxins enter the cytosol, and recognize and modify specific intracel-lular targets. According to the nature of the target and the type of modification, intracellular active toxins cause a dramatic alteration of cellular functions such as protein synthesis, cell homeostasis, cell cycle progression, vesicular traffic, and actin cytoskeletal rearrangements. Alternatively, invasive bacteria can directly inject toxins or virulence factors into target cells. This chapter is a com-parative overview of the molecular mechanisms of the main bacterial Exotoxins.

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  Strelkauskas' Microbiology

  A Clinical Approach

  • Beatrix Fahnert, Phoebe Lostroh(Authors)
  • 2023(Publication Date)
  • Garland Science

    (Publisher)

  Figure 5.16). Exotoxins are among the most lethal substances known: some Exotoxins are a million times more potent than the poison strychnine, which frequently features in detective fiction. Many of the genes that encode these toxins are carried on prophages or plasmids in the pathogens, which adds to the danger because these are mobile genetic elements that can transfer this genetic information from one bacterium to another.

  There are several types of exotoxin. They are often grouped via their structure or mode of action. Examples are cytotoxins, which kill cells that they come in contact with; neurotoxins, which interfere with neurological signal transmission; and enterotoxins, which affect the lining of the digestive system (

  Table 5.3

  ). We will now explore some of the more dangerous Exotoxins.

  Anthrax Toxin

  Anthrax toxin is a cytotoxin produced by the bacterium Bacillus anthracis, a Gram-positive rod commonly found in the soil of pastures. The toxin is made up of three parts: an edema factor (EF), a protective antigen (PA; a transmembrane factor also used for vaccine production), and a lethal factor (LF). Each bacterium produces the parts separately and assembles them on its surface in such a way that the complex is not yet toxic. The complex then leaves the surface and attaches to a host cell. Once attached to its target cell, the complex is endocytosed into a vesicle, where the low pH causes a conformational change in the complex, converting it to the toxic form. In this state, the protective antigen forms a pore in the vesicle membrane, and the edema and lethal factors temporarily change their shape so that they can squeeze into the host cell’s cytoplasm.

  Anthrax toxin interrupts the signaling capability of host macrophages and causes their death. It also interrupts the signaling capability of dendritic cells but does not kill them. However, even though they are still alive, the infected dendritic cells are no longer able to participate in the host defense against the infection. The importance of the loss of macrophage and dendritic cell function will become obvious in Chapters 15 and 16

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  Biotherapeutics

  Recent Developments using Chemical and Molecular Biology

  • Lyn Jones, Andrew J McKnight(Authors)
  • 2013(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  CHAPTER 8 Novel Therapeutic Agents from Bacterial Toxins JOHN A. CHADDOCK Syntaxin Ltd., Units 4–10 The Quadrant, Barton Lane, Abingdon, OXON, OX14 3YS, UK Email: [email protected] 8.1 Introduction Although it is difficult to arise at a consensus for the number of bacterial species on earth, it is well understood it represents one of the most diverse groups of living organisms and, from this diversity and the pressure to adapt to a variety of different environments, it is almost inevitable that evolutionary pressure has led to proteins with interesting and potentially useful properties. Bacterial protein toxins 1 are one such class of molecules with unique biology that can be both harmful and yet also useful. A toxin is defined as a poisonous substance, such as a protein, that is capable of causing disease when introduced into the body. The ability of bacteria to produce toxins is termed toxigenesis. There are two main types of bacterial toxins in lipopolysaccharides and proteins, and this chapter will focus on protein toxins; specifically extracellular difusable toxins (Exotoxins) that are produced from a subset of bacterial species. Released into the host by secretion or bacterial cell lysis, Exotoxins act enzymatically within a host cell or by direct action with host cells leading to a stimulation of host cell responses. This chapter will focus on bacterial protein toxins that act intracellularly within a host cell, leading to a modification of host cell biology. RSC Drug Discovery Series No. 36 Biotherapeutics: Recent Developments using Chemical and Molecular Biology Edited by Lyn H. Jones and Andrew J. McKnight r The Royal Society of Chemistry 2013 Published by the Royal Society of Chemistry, www.rsc.org 224 This modification can be lethal to the intoxicated cell, leading to local cellular destruction and, if the intoxication is widespread, subequent host death.

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  Microbial Toxins in Dairy Products

  • Adnan Y. Tamime(Author)
  • 2016(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  3 Bacterial Toxins – Structure, Properties and Mode of Action J.W. Austin

  3.1 Background

  Bacteria produce a diverse range of molecules that exert toxic effects on a variety of fundamental eukaryotic cell processes. Toxins are an essential virulence factor of pathogenic bacteria. It is through toxins that these pathogens are able to affect host cells, contributing to disease. Pathogenic strains of Escherichia coli can produce several toxins including endotoxin, heat labile enterotoxin, heat stable enterotoxin, Shiga‐toxin, cytolethal distending toxin, and cytotoxin necrotising factors (Kaper et al., 2004). Staphylococci produce a whole range of toxins and extracellular enzymes, such as proteases, a hyaluronidase, a lipase and a nuclease that facilitate tissue destruction and spreading, membrane‐damaging toxins that cause cytolytic effects on host cells and tissue damage, four types of toxins effective against leukocytes, exfoliative toxins, and superantigens that contribute to the symptoms of septic shock (Berube & Wardenburg, 2013; Bukowski et al., 2010; Hennekinne et al., 2012; Otto, 2014).

  Toxins produced by enteropathogenic or enteroxigenic bacteria come into contact with host cells through three primary mechanisms (Popoff, 2011). Several bacterial species naturally occurring in food can grow and secrete toxins directly in the food. The bacterial toxins are ingested with the food, causing foodborne intoxication. In the case of botulism, this has been referred to as “primary intoxication” (Simpson, 2004). Other examples of bacteria causing this type of foodborne illness include Bacillus cereus (both diarrheal toxins and emetic toxin) and Staphylococcus aureus. Foodborne intoxications typically display short incubation times and, with the exception of botulism, recovery occurs within 24–36 h after ingestion of the toxin. A second type of mechanism involves ingestion of bacteria with the food, followed by release of the toxin in the intestinal lumen without bacterial adherence to epithelial cells. An example of this is Clostridium perfringens, which releases an enterotoxin when large numbers of ingested cells sporulate in the gastrointestinal tract, without colonisation. The third mechanism includes bacterial pathogens that adhere to the intestinal epithelial cells and produce toxins that directly affect the intestinal epithelial cells, often by direct secretion into the epithelial cells. Examples include Vibrio cholera (cholera toxin) and verotoxigenic E. coli (verotoxin or Shiga‐toxin). While this classification into three mechanisms holds true for most bacterial toxins, exceptions exist including colonisation of the intestinal lumen by Clostridium difficile followed by production of toxins A and B during the infection. In the case of infant botulism and adult intestinal botulism, this has been referred to as toxicoinfection (Sonnabend et al., 1987) or as intestinal toxemia (Arnon, 1995; Fenicia et al., 2007; Sheppard et al., 2012). Alternatively, intestinal epithelial cells may be invaded by Listeria monocytogenes

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  Bacterial Toxins

  Tools in Cell Biology and Pharmacology

  • Klaus Aktories(Author)
  • 2008(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Preface Remarkable progress has been made in the field of bacterial protein toxins: the molecular mechanisms of several toxins (e.g., clostridial neurotoxins and cytotoxins) whose modes of action were obscure until recently, have been elucidated during the last years. This prog- ress in cellular and molecular toxinology not only provides insights into the mode of action of important virulence factors and patho- mechanisms of diseases, but also has a maior impact on the under- standing of regulation and mechanisms of eukaryotic cell functions which are disturbed by the toxins. These spectacular advances mainly depend on a bidirectional approach: cell biological methods are suc- cessfully applied for elucidation of the molecular mechanisms of bac- terial toxins and, on the other hand, the bacterial toxins are used as powerful, extremely valuable tools to unravel mechanisms in molecu- lar cell biology. The reasons for using toxins as tools are evident. First, they are very potent agents, a fact which is often based on their enzymatic activity (e.g., clostridial neurotoxins, which act as endoproteases, are the most potent agents known). Second, the high selectivity and specific- ity of the toxins are most important for their use as tools. Cell selectiv- ity may be due to specific receptor binding (e.g., selectivity of neuro- toxins). The high specificity of action depends on the extremely spe- cific recognition of target proteins. Finally, bacterial protein toxins seem to be maximally efficient agents. In most cases the toxins strike the eukaryotic cell at a crucial site indicating modification of impor- tant eukaryotic components or signaling pathways. Therefore, the toxins are excellent tools to recognize the biological importance of a cellular component, or the biological significance of a signal pathway altered by the toxins. This book is intended to establish and facilitate the use of bacterial protein toxins as tools in cell biology and pharmacology.

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  Staphylococci in Human Disease

  • Kent B. Crossley, Kimberly K. Jefferson, Gordon L. Archer, Vance G. Fowler, Kent B. Crossley, Kimberly K. Jefferson, Gordon L. Archer, Vance G. Fowler, Jr.(Authors)
  • 2009(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Chapter 6 Exotoxins Patrick M. Schlievert 1 , John K. McCormick 2 , Gregory A. Bohach 3 and Douglas H. Ohlendorf 4 1 Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, USA 2 Department of Microbiology, University of Western Ontario, London, Ontario, Canada 3 Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, Idaho, USA 4 Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA enterotoxin serotypes SEA, SEB, SEC n , SED, SEE, SEG, and SEI; staphylococcal enterotoxin-like serotypes SEl-H and SEl-J to SEl-V; and the streptococcal pyrogenic Exotoxins (SPEs) synthesized by group A Streptococcus strains and certain other β -hemolytic streptococci [1]. The superanti-gen SEF was renamed TSST-1 and therefore the SEF serotype has been retired [2]. These toxins are all charac-terized by their shared capacities to induce high fever, enhance host susceptibility to the lethal effects of endotoxin, and induce T-lymphocyte proliferation as superantigens [1,3]. All share the ability to cause serious life-threatening toxic shock syndromes and related illnesses. The staphylo-coccal enterotoxins possess the additional property, not shared with other members of the family, of causing emesis when given orally to monkeys [4]. Thus, staphylococcal enterotoxins are major causes of food poisoning, charac-terized by vomiting and diarrhea with onset 2– 8 hours after ingestion of preformed toxin in contaminated food. The staphylococcal enterotoxin-like proteins are related to staphylococcal enterotoxins in both primary amino acid sequence and three-dimensional structure, but the staphy-lococcal enterotoxin-like proteins either lack emetic activity or have not been tested [5]. Table 6.1 summarizes the biological activities of these toxins.

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  Toxins in Food

  • Waldemar M. Dabrowski, Zdzislaw E. Sikorski(Authors)
  • 2004(Publication Date)
  • CRC Press

    (Publisher)

  8 Bacterial Toxins Waldemar D a ˜ browski and Dagmara M e ˜ drala C ONTENTS 8.1 Introduction 8.2 Clostridium botulinum 8.2.1 Botulin Toxins 8.2.2 Clostridium botulinum in the Environment 8.2.3 Clostridium botulinum in Food 8.2.4 Detection of Botulin Toxins 8.3 Staphylococcus aureus 8.3.1 Staphylococcal Toxins 8.3.2 Mechanism of Toxin Action 8.3.3 Enterotoxins and Food Products 8.3.4 Detection of Staphylococcal Toxins 8.4 References 8.1 INTRODUCTION The reported number of cases of bacterial foodborne poisonings (BFBP) and the deaths they cause worldwide is enormous, both in developing and industrialized countries. In the U.S. alone, each year 76 million foodborne illnesses are reported and 325,000 patients are hospitalized, of which 5000 die. The etiological agent is identified only in 18% of cases, the rest remain undiagnosed or misdiagnosed (Mead et al., 1999). The number of human pathogens found in food is limited. They may be divided into three groups (Table 8.1): Group I contains bacteria that do not produce typical toxins, and the diseases they cause are a result of their outgrowth within a host organism. Such microorganisms produce molecules that provide a defense against host immunological mechanisms and transmission within the invaded organism. When the bacteria reach intestinal epithelium, they penetrate tissues by the outgrowth in cell cytosol or vacuoles. Group II includes bacteria that produce toxins responsible for the course of disease during gastrointestinal invasion. Disease symptoms are the result of cell destruction caused by extracellular toxins and by elements present in the cell wall, e.g., fimbriae. Such toxins are not 192 Toxins in Food Table 8.1 Bacterial foodborne pathogens. Group I Group II Group III Organism Effects Organism Toxins and effects Organism Toxins Shigella Colonization and invasion of epithelial cells in large intestine Replication in cytoplasm Aeromonas sp.

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