Gastrointestinal Infections: Toxins

C. Botulinum
1. Neurotoxin: Inhibits acetylcholine release from nerve endings, flaccid paralysis
  1. Heavy (100kDa) & Light Chain (50kDa, metalloprotease, HexxH zinc-binding motif, cleaves SNARE complex, ie SNAP-25, synaptobrevin, or syntaxin)
2. Types A-G but food-bourne usually A,B,D, E (marine)
3. Therapy= antitoxins to mop up free toxin
4. Difficult to diagnose: Similar to stroke symptoms. Need to isolate toxin from faeces/CSF/serum, takes 2+ days to show!
  1. Mouse bioassay (4 days), new PCR developed
5. G+ve, spore forming (survive high temps), anaerobe
6. Outbreaks through contaminated food- preserving/canning process inadequate
7. Incubation: 6hrs-16days
8. Vaccine for high risk workers,e.g. scientists
9. Infant botulism: Linden flowers implicated, natural sedative
S. aureus
1. G+, coccus, facultative anaerobe
2. Stable over range of pH/salt/temps
3. Staph enterotoxin, heat-resistant
4. Abdominal pain, vomiting, fever
5. Catalase +ve, coagulase/DNAse +ve
6. 20-100ng enough to cause infection
7. Protein-rich foods, e.g. dairy/meat
8. Incubation: 1-6hrs, infection:<48hrs
9. Enter text here
B. cereus
1. Cereulide (emetic toxin), cyclic dodecadepsipeptide
  1. Highly resistant to acid/proteolysis, heat
  2. Bind 5HT3 receptor on vagus afferents (nerve fibres) to stimulate sickness
  3. Inhibits fatty acid oxidation in mitochondria, possible liver toxicity
  4. Encoded on a megaplasmid, via ces genes
  5. PlcR regulated expression
2. 103-108 infectious dose (high)
3. Can cause meningitis, UTIs, RTIs, HAIs!
  1. RTIs: carries anthracis pX01 plasmid (but no pX02- required for capsule+positive regulator of toxin genes on pX01)
  2. HAIs: amongst immunosuppressed patients, equipment contaminated e.g. ventilators, intravenous catheters, etc
  3. Meningitis, meningoencephalitis, brain abscess, etc. Abdominal pain before bacteremia-->brain. Risk factors include intrathecal induction chemotherapy
  4. UTIs: Contaminant on catheter (forms biofilm)--->pyelonephritis.
4. Diarhoeal toxins
  1. Tripartite (Cytotoxin K & Nonhaemolytic Enterotoxin)
    Anmerkungen:
    - NHe most dominant!!
    1. L1, L2 (lytic) & B (binding) subunits (CytK), NHeA, NHeB, NHeC (NHe)
    2. NHe= pore former
  2. Oligomeric B-barrel pore-forming (Haemoysin bl & CytK)
  3. Cerelysin O
  4. Haemolysin II
    1. HlyIIR, dimeric transcriptional regulator (repressor)
  5. InhA2
  6. phospholipase C
5. G+ve, facultative-to-aerobic, spore-forming (resistant to gamma radiation/pasteurisation), non-mannitol fermentor
6. Some strains produce negligible amounts of toxin & authorised for use as probiotic!
7. Vomiting infection: 8-10hours, diarrhoeal infection: 20-36hrs
C.perfringens
1. G+ve, spore-forming, anaerobic
2. IN NORMAL FAECAL FLORA
3. Incubation: 8-14hrs, infection: 24hrs
4. Peaks in autumn (stews)
5. Toxins
  1. CPE (enterotoxin)
    1. Bind claudin -3, -4, -8, -14
      1. Oligomerises into hexamer (CH1)
        Influx of Ca2+ into cell--> apoptotic pathway
      2. CH2
        Internalises occludin
        Histopathologic damage to cells--> diarrhoea
    2. Cytoplasmic C and N termini, 4 transmembrane domains
  2. Iota toxin
    1. ADP-ribosyltransferase
    2. CD44 binding implicated
6. Non-motile
V. cholerae
C. Difficile

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Gastrointestinal Infections: Toxins

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