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36 Cards in this Set

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What is the definition of microbial toxins
Macromolecular products of microbes that harm susceptible animals, usually by altering cellular structure or function. They are very potent
What are some important things to remember about toxins
Some toxins cause specific clinical manifestations; Other toxins contribute to pathogenesis without causing unique signs and symptoms; Toxin-mediated diseases cause significant morbidity and mortality; Certain toxins have the potential to be used as agents of bioterrorism
Where in bacteria are genes for toxin production often present
Mobile genetic elements, such as bacteriophages, plasmids or transposons
Genes for toxins and other virulence factors in pathogenic microbes are often coordinately regulated by what
Environmental signals. Microbes can use two-component regulatory systems to detect when they are in an animal host and express virulence factors appropriate for growth in host
What are the composition and properties of toxins
Most bacterial toxins are proteins. They are heat labile, immunogenic, and neutralized by specific antibodies
What are the mechanisms of action in toxins
Facilitate spread through tissue; damage cellular membranes; Stimulate production of excessive amounts of cytokines; Inhibit protein synthesis; Activate second messenger pathways; inhibit release of neurotransmitters; modify cytoskeleton of target cell
What are hyaluronidase, collagenase, elastase, deoxyribonuclease, and streptokinase
Toxic enzymes that break down the extracellular matrix or degrade cellular debris in necrotic tissue
What are membrane-damaging toxins sometimes called
Hemolysins, because they lyse erythrocytes; however, they are usually active against other cell types and are more accurately designated as cytolysins
What do lecithinases do
Degrade essential components of cell membranes
What are pyrogenic exotoxins? Name three
Family of related proteins that includes the erythrogenic toxins of Streptococcus pyogenes, the enterotoxins of Staphylococcus aureus, and toxic shock syndrome toxin of S. aureus.
Pyrogenic exotoxins are involved in pathogenesis of what
Scarlet fever, food poisoning, and toxic shock syndrome
Why are pyrogenic exotoxins designated as superantigens
They can activate populations of T cells that are specific for many different antigens. They are the most potent known activators of T cells
Besides activating T cells, what else do superantigens do
They enhance susceptibility to LPS, suppress B cell mediated responses, and stimulate cytokine production by macrophages
How do pyrogenic exotoxins work
They bind to MHC class II on APCs, which then bind to specific V chains on T cells at a site distant from the T cell receptor. This stimulates production of excessive amounts of cytokines (IL-2, IFN-gamma)
What is the mechanism of action of Diphtheria toxin and Pseudomonas aeruginosa exotoxin A
They inactivate elongation factor 2 (EF-2), which is required for peptide chain elongation.
What are Diphtheria toxin and Pseudomonas aeruginosa exotoxin A
ADP ribosyltransferases that transfer adenosine diphosphate ribose from NAD to EF-2, inactivating it
What are Shiga toxins of Shigella dysenteria and E. coli and the plant toxin ricin
Highly specific RNA N-glycosidases that remove one particular adenine residue from the 28S RNA of the 60S ribosomal subunit
Define cytotonic
Toxins that alter the functions of target cells without killing them
What are heat-labile enterotoxins of Vibrio cholerae and E. coli
ADP ribosyltransferases that activate cell membrane-associated adenylate cyclase by ADP-ribosylating the Gs protein of the cyclase complex. This increases intracellular cAMP in enterocytes and causes secretory diarrhea
What is pertussis toxin
An ADP-riboslytransferase that activates adenylate cyclase by deactivating inhibitory G protein of the cyclase complex.
What does heat-stable enterotoxin I (ST-I) of E. coli do
Activates guanylate cyclase, increasing intracellular cGMP in enterocytes and causing diarrhea
What are the anthrax edema factor component of anthrax toxin and the toxin of Bordella pertussis
Adenylate cyclase enzymes that enter target cells and increase intracellular cAMP. Activated by calmodulin and calcium in target cells
How does Botulinun toxin work
Causes flaccid paralysis by inhibiting release of acetylcholine at myoneural junctions
How does tetanus toxin work
Inhibits release of neurotransmiter from inhibitory interneurons in the spinal cord, resulting in muscular contraction and tetany
What is the mechanism of action of Botulinum toxin and tetanus toxin
They have zinc-dependent endopeptidases that recognize specific proteins of the neuroexocytosis apparatus and cleave them at particular sites
What does Clostridium difficile cytotoxin (toxin B) do
Causes disaggregation of actin filaments by glucosylating RhoA, one of the small GTP-binding proteins
What are the characteristics of toxins that act extracellularly or on plasma membranes
They are diverse in structure and functions. Their specificity is usually determined directly by the target of their action
What are the characteristics of toxins that have intracellular targets
They are usually bifunctional proteins; Normal membrane constituents are used by toxins as receptors; Susceptibility or resistance is often determined by the presence or absence of specific receptors; Toxins usually enter by endocytosis
What is the receptor for diphtheria toxin
The heparin-binding EGF-like growth factor precursor
What is the receptor for cholera toxin and related heat-labile enterotoxins
Ganglioside GM1
What is the membrane receptor for Shiga toxins of Shigella dysenteriae and E. coli
Glycolipid Gb3
How do Shiga toxin, exotoxin A, cholera toxin, and pertussis toxin enter the cytosol
They follow an endocytic pathway through the trans-Golgi network and endoplasmic reticulum
What are some of the ADP-ribosylating toxins
Heat-labile enterotoxins, pertussis toxin, diphtheria toxin, exotoxin A of P. aeruginosa. They all catalyze transfer of ADP-ribose from NAD to acceptor proteins
What are some of the principles of Prophylaxis and therapy of toxin-mediated disease
Antitoxic antibodies neutralize specific toxins and prevent their toxic effects; Toxoids retain immunogenicity but lack toxicity; Passive immunization involves administration of antibodies; Active immunization involves administration of an antigen; a primary series of immunization and periodic booster doses are required to achieve protective levels
What is used to immunize children against tetanus, diphtheria and pertussis
Tetanus and diphtheria toxoids combined with acellular Bordetella pertussis vaccine
What are immunotoxins
Hybrid molecules that contain the active A fragment of toxin fused with specific ligands. They are designed to kill tumor cells that display specific receptors