Gastrointestinal Infections: Toxins

Gastrointestinal Infections: Toxins

1. C. Botulinum

   • Neurotoxin: Inhibits acetylcholine release from nerve endings, flaccid paralysis
     • Heavy (100kDa) & Light Chain (50kDa, metalloprotease, HexxH zinc-binding motif, cleaves SNARE complex, ie SNAP-25, synaptobrevin, or syntaxin)
   • Types A-G but food-bourne usually A,B,D, E (marine)
   • Therapy= antitoxins to mop up free toxin
   • Difficult to diagnose: Similar to stroke symptoms. Need to isolate toxin from faeces/CSF/serum, takes 2+ days to show!
     • Mouse bioassay (4 days), new PCR developed
   • G+ve, spore forming (survive high temps), anaerobe
   • Outbreaks through contaminated food- preserving/canning process inadequate
   • Incubation: 6hrs-16days
   • Vaccine for high risk workers,e.g. scientists
   • Infant botulism: Linden flowers implicated, natural sedative

2. S. aureus

   • G+, coccus, facultative anaerobe
   • Stable over range of pH/salt/temps
   • Staph enterotoxin, heat-resistant
   • Abdominal pain, vomiting, fever
   • Catalase +ve, coagulase/DNAse +ve
   • 20-100ng enough to cause infection
   • Protein-rich foods, e.g. dairy/meat
   • Incubation: 1-6hrs, infection:<48hrs
   • Enter text here

3. B. cereus

   • Cereulide (emetic toxin), cyclic dodecadepsipeptide
     • Highly resistant to acid/proteolysis, heat
     • Bind 5HT3 receptor on vagus afferents (nerve fibres) to stimulate sickness
     • Inhibits fatty acid oxidation in mitochondria, possible liver toxicity
     • Encoded on a megaplasmid, via ces genes
     • PlcR regulated expression
   • 103-108 infectious dose (high)
   • Can cause meningitis, UTIs, RTIs, HAIs!
     • RTIs: carries anthracis pX01 plasmid (but no pX02- required for capsule+positive regulator of toxin genes on pX01)
     • HAIs: amongst immunosuppressed patients, equipment contaminated e.g. ventilators, intravenous catheters, etc
     • Meningitis, meningoencephalitis, brain abscess, etc. Abdominal pain before bacteremia-->brain. Risk factors include intrathecal induction chemotherapy
     • UTIs: Contaminant on catheter (forms biofilm)--->pyelonephritis.
   • Diarhoeal toxins
     • Tripartite (Cytotoxin K & Nonhaemolytic Enterotoxin)
       • NHe most dominant!!
       • L1, L2 (lytic) & B (binding) subunits (CytK), NHeA, NHeB, NHeC (NHe)
       • NHe= pore former
     • Oligomeric B-barrel pore-forming (Haemoysin bl & CytK)
     • Cerelysin O
     • Haemolysin II
       • HlyIIR, dimeric transcriptional regulator (repressor)
     • InhA2
     • phospholipase C
   • G+ve, facultative-to-aerobic, spore-forming (resistant to gamma radiation/pasteurisation), non-mannitol fermentor
   • Some strains produce negligible amounts of toxin & authorised for use as probiotic!
   • Vomiting infection: 8-10hours, diarrhoeal infection: 20-36hrs

4. C.perfringens

   • G+ve, spore-forming, anaerobic
   • IN NORMAL FAECAL FLORA
   • Incubation: 8-14hrs, infection: 24hrs
   • Peaks in autumn (stews)
   • Toxins
     • CPE (enterotoxin)
       • Bind claudin -3, -4, -8, -14
         • Oligomerises into hexamer (CH1)
           • Influx of Ca2+ into cell--> apoptotic pathway
         • CH2
           • Internalises occludin
           • Histopathologic damage to cells--> diarrhoea
       • Cytoplasmic C and N termini, 4 transmembrane domains
     • Iota toxin
       • ADP-ribosyltransferase
       • CD44 binding implicated
   • Non-motile

5. V. cholerae

6. C. Difficile