Neurotoxins

Question 1

Clostridia

Answer 1

• Anaerobic: can’t use O2 as final e- acceptor
  
  • strict anaerobe: unable to breakdown H2O2 b/c no catalase
• Gram positive
• Spore forming rods
• Makes toxin in botulism and tetanus

Question 2

3 diseases caused by Botulism

Answer 2

1. Food poisoning: eat food w/ preformed toxins
2. Wound botulism: toxin contaminated traumatic wounds
3. Infant botulism: sores go to vegetative rods in infant GI
   
   • Not seen in adults b/c don’t have redox potential

Question 3

Botulinum Toxin Characteristics

Answer 3

• 7 types: A-G
• A, B, E most common in humans
• One of most potent poisons
• Toxin destroyed at 100 degrees C for 10 min
  
  • Spores are heat resistant

Question 4

Botulinum Toxin Mode of Action

Answer 4

• Interferes w/ Acetylcholine release at NMJ
• Causes flaccid paralysis
• Zinc dependent endoprotease
  
  • cleaves the SNARE proteins of vesicles preventing release
  • Takes a long time to regenerate vesicles

Question 5

Botulism Food Poisoning

Answer 5

• Type A, B, or E
• Spores contaminate canned foods
  
  • alkaline pH lets spores germinate
• Anaerobic conditions allow vegetative form to produce toxin
• Toxin absorbed and cause neurotoxicity
• Symptoms: 12-36h after ingestion
  
  • Dry mouth/ trouble swallowing
  • visual and speech disturbances
  • Descending paralysis
  • No fever or GI issues
• High mortality due to respiratory paralysis or cardiac arrest

Question 6

Wound Botulism

Answer 6

• Rare: C. botulinum in traumatic wound
• Get toxic effects from growth in wounds
• Seen in heroin users

Question 7

Infant Botulism

Answer 7

• GI tract gets colonized w/ C. botulinum
• Honey implicated as carrier of type B
• Spores become rods due to redox potential in infant gut not seen in adults
• Floppy baby syndrome

Question 8

Treatment

Answer 8

• Adult: heptavalent antitoxin agains all 7 types
  
  • Prepared in horses
• Infant: babyBIG: botulism immune globulin
  
  • Human derived botulism antitoxin antibodies

Question 9

BoTox for Medical Use

Answer 9

• Muscle relaxation in cases of eyelid paralysis, stroke, or migraines
• cosmetic use to remove wrinkles

Question 10

Tetanus

Answer 10

• Potent neurotoxin: tetanospasmin
  
  • Cleaves proteins in neurotransmission
  • Inhibits release of glycine
• Only one antigenic tyoe
• Metaloprotease
• C. tetani causes
  
  • Soil and horse feces
• Often fatal
• Vaccine
• Tension spastic paralysis

Question 11

Tetanus Toxin Mode of Action

Answer 11

• Cleaves VAMP (synaptobrevin)
• Prevents release of glycine from inhibitory interneurons
• Overstimulation of muscle: spasms

Question 12

Tetanus Clinical Presentation

Answer 12

• trismus (lockjaw)
• risus sardoicus: characteristic facial expression
• Stiff neck
• Difficulty swallowing
• Rigid abdominal muscles
• Involvement of other muscles
• Death occurs due to interference w/ respiration

Question 13

Tetanus treatment

Answer 13

• Antitoxin: doesn’t act on already bound toxin though
• Muscle relaxants & sedation
• Assisted ventilation
• Prevent w/ immunization