Bacteriology lecture 17 Bacterial toxins
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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