Toxins Flashcards
(21 cards)
Describe v.cholerae
Gram-negative, comma-shaped, motile bacterium.
Transmitted via the fecal-oral route, often through contaminated water or food
Endemic in areas with poor sanitation.
Symptoms:
• Acute watery diarrhea, copious vomiting, lower leg cramps.
• Rapid fluid and electrolyte loss.
Describe the cholera toxin
Cholera Toxin (CT):
• AB toxin (A: catalytic, B: binding subunit).
• Produced by O1 and O139 serotypes.
• Results in increased cAMP, activation of protein kinase A, phosphorylation of CFTR, and massive efflux of Cl⁻ (and water) into the intestinal lumen.
• Inhibits Na⁺ and K⁺ reabsorption, causing severe diarrhea.
Describe the action of the cholera toxin
Binds to GM1 ganglioside receptor on enterocytes, is endocytosed, and trafficked to the ER.
• A subunit activates the G protein and locks it in the GTP configuration , leading to persistent activation of adenylate cyclase.
• Results in increased cAMP, activation of protein kinase A, phosphorylation of CFTR, which enables massive efflux of Cl⁻ (and water) into the intestinal lumen.
• Inhibits Na⁺ and K⁺ reabsorption, causing severe diarrhea.
Describe the metabolism of the cholera toxin
Metabolism & Excretion:
• A subunit is eventually degraded by the proteasome.
• Diarrhea facilitates pathogen transmission; treatment focuses on rehydration and electrolyte replacement.
Describe STEC
STEC (Shiga Toxin-Producing E. coli):
• Major reservoir: ruminants.
• Transmission through contaminated food, water, or direct animal contact.
• Very low infectious dose (100 cells)
Describe STEC action and shiga toxin action
Attachment & Toxin Release:
• STEC attaches to enterocytes via fimbriae and TIR/intimin interaction.
• Shiga toxin (AB type) is released, binds to Gb3/Gb4 receptors, and is endocytosed.
Mechanism:
• Retrograde transport to Golgi and ER; A subunit enters cytosol.
• Inhibits protein synthesis by removing adenine from 28S rRNA in ribosomes.
• Leads to cell death (apoptosis), inflammation, and villi effacement (bloody diarrhea).
• Systemic absorption can damage kidneys (hemolytic uremic syndrome, HUS) and CNS.
Why are kidney cells especially vulnerable to STEC
High Gb3 expression
Describe the effect of STEC/Stx on the immmune system
• Induces cytokine production, inflammation, and may be transported in the bloodstream by immune cells.
Describe c.botulinum
C. botulinum:
• Gram-positive, spore-forming, obligate anaerobe.
• Spores survive in improperly processed foods; infants and young children are especially susceptible.
Routes of Exposure:
• Ingestion (contaminated food), inhalation (rare), or wound contamination.
Describe the action of c.botulinum and the botulinum toxin
Mechanism at Neuromuscular Junction:
• Normally, SNARE proteins mediate vesicle fusion and acetylcholine (ACh) release for muscle contraction.
• Botulinum toxin is endocytosed by nerve cells.
• Light chain cleaves SNARE proteins, preventing ACh release, resulting in flaccid paralysis.
How are AB toxins excreted
Excretion of AB Toxins
• Large AB toxins (Shiga, Botulinum) are not filtered by the kidneys. (Too large)
• Likely metabolized in the liver to inactive fragments, which are then excreted via the urea cycle or used for biosynthesis.
Which two toxins are systematically absorbed
Shiga and botulinum
What is the main effect of the cholera toxin
Watery diarrhoea
What is the main effect of the shiga toxin
Cell death, HUS, bloody diarrhea
What is the main effect of the botulinum toxin
Flaccid paralysis
What is the main mechanism of action of the cholera toxin
Activates cAMP/PKA, stimulates Cl⁻ and water efflux
What is the main mechanism of action of the shiga toxin
Inhibits protein synthesis (ribotoxicity)
What is the main mechanism of action of the botulinum toxin
Blocks ACh release by cleaving SNARE proteins
What is the target site of the cholera toxin
Intestinal epithelium
What is the target site of the shiga toxin
Intestinal and kidney cells
What is the target site of the botulinum toxin
Neuromuscular junction
