questions 3

Exotoxins

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Topic updated on 01/09/17 10:27am

 

 
Exotoxin Overview
  • Exotoxins are proteins released by both Gram-positive and Gram-negative bacteria
    • all major Gram-positives produce exotoxin
      • except Listeria monocytogenes (produces endotoxin)
    • exotoxins are not heat stable
      • destroyed rapidly at 60°C
        • except Staphylococcal enterotoxin
  • Exotoxin types and examples of each
    • enterotoxins
      • act on the GI tract to cause diarrhea
      • cause osmotic pull of fluid into the intestines
      • 2 mechanisms by which enterotoxins cause disease
        • infectious diarrhea
          • bacteria colonize GI tract and continuously secrete enterotoxin
          • diarrhea continues until infection is cleared
          • examples
            • Vibrio cholera
            • E. coli
            • Campylobacter jejuni
            • Shigella dysenteriae
        • food poisoning 
          • bacteria grow in food and release enterotoxin into food
          • less than 24 hours of diarrhea and vomiting
          • examples
            • Bacillus cereus
            • Staphylococcus aureus
    • neurotoxins
      • act on the nerves or NMJ to cause paralysis
      • Clostridium tetani
    • pyrogenic exotoxins
      • stimulate release of cytokines
      • cause rash, fever, toxic shock syndrome
      • S. aureus, Streptococcus pyogenes
    • tissue invasive exotoxins
      • enzymes that destroy tissue to allow bacteria to invade the host
      • "SHiN" bacteria
      • group A streptococcus
  • cAMP inducers
    • V. cholerae, Bordetella pertussis, and E. coli (ETEC)
      • via ADP ribosylation
    • Bacillus anthracis 
      • edema factor is an adenylate cyclase
  • A-B ADP ribosylation
    • Corynebacterium diphtheriae and Pseudomonas
    • Vibrio cholerae
    • E. coli
    • Bordetella pertussis
  • S. aureus secretes multiple types of exotoxins as described below
    • superantigen TSST-1
    • enterotoxin
    • exfoliatin
    • protein A
Enterotoxins
  • V.cholerae toxin
    • AB toxin
      • A subunit is active
    • ADP ribosylation of G protein stimulates adenylyl cyclase
      • permanently activates Gs
    • ↑ pumping of Cl- into gut and ↓ Na+ absorption
    • H2O moves into gut lumen
    • causes voluminous rice-water diarrhea
    • "turns the 'on' on"
  • E. coli (ETEC) 
    • heat-labile toxin stimulates adenylate cyclase → ↑ cAMP
      • increase Cl- secretion and H2O efflux
      • just like cholera
    • heat-stable toxin stimulates guanylate cyclase → ↑ cGMP
      • decrease resorption of NaCl and H2O
    • both cause watery diarrhea
    • "Labile like the Air, stable like the Ground"
Neurotoxins
  • C. tetani
    • blocks the release of inhibitory neurotransmitters GABA and glycine
    • causes "lockjaw"
    • zinc-dependent protease
  • C. botulinum
    • blocks the presynaptic release of acetylcholine at the NMJ
    • causes anticholinergic symptoms, CNS paralysis (especially cranial nerves)
    • spores found in honey (causes floppy baby)
    • improperly canned food contains preformed toxin (effects adults)
    • zinc-dependent protease
Pyrogenic exotoxins
  • S. aureus
    • TSST-1 superantigen causes toxic shock syndrome (fever, rash, shock)
      • binds directly to MHC II and T cell receptor simultaneously, activating large numbers of T cells to stimulate release of IFN-γ, IL-2, IL-1
    • additionally, S. aureus secretes
      • enterotoxins
        • cause food poisoning
      • exfoliatin
        • causes staphylococcal scalded skin syndrome
      • protein A
        • binds Fc region of Ig
        • prevents opsonization and phagocytosis
  • S. pyogenes
    • scarlet fever-erythrogenic toxin causes toxic shock-like syndrome
    • streptolysin O is a hemolysin
    • antigen for ASO antibody
      • used in the diagnosis of rheumatic fever
Tissue invasive exotoxins
  • S. pneumoniae, Haemophilus influenza type B, and Neisseria
    • all secrete IgA protease in order to colonize respiratory mucosa
      • enzyme that cleaves IgA
    • recall that these 3 bacteria are the "SHiN" encapsulated bacteria
  • Group A streptococcus
    • M protein
      • helps prevent phagocytosis
Miscellaneous exotoxins
  • Shiga toxin
    • inactivates mammalian 60S ribosomal subunit
      • prevents binding of tRNA to 60S subunit
    • Shiga toxin released by Shigella
    • Shiga-like toxin (similar mechanism) released by EHEC
      • active A subunit + 5 binding B subunits
      • plasmid transmitted to E. coli by temperate bacteriophage
  • B. pertussis
    • AB toxin
    • increases cAMP by inhibiting Gαi
    • causes whooping cough
    • "turns the 'off' off"
    • inhibits chemokine receptor, causing lymphocytosis
    • impairs phagocytosis by host
  • B. anthracis toxin
    • induces edema factor, a bacterial adenylate cyclase (↑ cAMP)
  • Corynebacterium diphtheriae
    • AB toxin
      • B subunit binds cardiac and neural cells
    • A subunit inactivates elongation factor 2 (EF-2) → inhibit host cell protein synthesis → death
      • via ADP ribosylation
      • EF-2 is needed for peptide chain translocation on the ribosome during translation
      • also seen with Pseudomonas exotoxin A
    • causes pharyngitis and "pseudomembrane" in throat
  • C. difficile
    • A-B cytotoxin kills enterocytes and causes pseudomembranous colitis
      • toxin A
        • attracts neutrophils, causing inflammation
        • causes loss of water into gut lumen
      • toxin B
        • actin depolymerization
        • loss of cytoskeleton integrity
  • C. perfringens
    • α toxin (also known as phospholipase C or lecithinase) causes gas gangrene
      • get double zone of hemolysis on blood agar
      • degrades lecithin, a component of cell phospholipid membranes
      • causes loss of cell membrane integrity
      • leads to membrane destruction, cell death, necrosis, hemolysis


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Qbank (2 Questions)

TAG
(M1.MC.75) A 19-year-old man returns from travel in South America. He presents complaining of profuse, watery diarrhea. You suspect the causative organism to be Enterotoxigenic E. coli. What is the mechanism by which this organism causes diarrhea? Topic Review Topic

1. Blocks the release of inhibitory neurotransmitters GABA and glycine
2. Blocks the presynaptic release of acetylcholine at the neuromuscular junction
3. Inactivates mammalian 60S ribosomal subunit
4. Stimulates release of cytokines
5. Stimulates adenylate cyclase (increasing cAMP)

PREFERRED RESPONSE ▶
TAG
(M1.MC.75) A 22-year-old woman comes to the urgent care clinic with sudden onset of severe vomiting. She had been at a picnic with her boyfriend a few hours earlier, enjoying barbecue, potato salad, and cake. Shortly thereafter, she began vomiting and has vomited 5 times in the last 3 hours. She has no prior history of symptoms. After a few hours of observation, her symptoms abate, and she is safely discharged home. Which of the following is the most likely cause of her vomiting? Topic Review Topic

1. Viral infection
2. Hepatitis
3. Gallstones
4. Toxin ingestion from spore-forming organism
5. Toxin ingestion from non-spore-forming organism

PREFERRED RESPONSE ▶
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