Lecture 35ish: Cholera And Cystic Fibrosis

Question 1

Cholera

Answer 1

• Caused by Vibrio cholerae, a comma-‐shaped, Gram-negave bacterium
• Acquired by ingesng food or water contaminated by fecal maer from paents or carriers
• Shellfish are natural reservoirs
•   Organisms adhere to intesnal mucosa of small intestine and secrete the toxin choleragen
• Warning, this is one of those “not everything transfers perfectly to brainscape slides”.
• Presence of toxin results in massive loss of water and electrolytes
  –  production of “rice-‐water stools”
• Diagnosis –  culture from feces with subsequent identification by agglutination reactions
• Treatment, control, and prevention
  –  oral rehydration and antibiotic therapy

Question 2

Cholera Toxin

Answer 2

• Choleragen
  –  Oligomeric, AB toxin
• Part A, enzymatic - 1 copy
  -  Part B, receptor binding –  5 copies
• See Slides 13-17

Question 3

Cyclic AMP (cAMP)

Answer 3

• cAMP acvates cyclic AMP-‐dependent protein kinase A (PKA)
  –  Binding of cAMP to the regulatory protein releases the inhibion of PKA
  –  Serine/threonine kinase
• See slides 18-20

Question 4

Cysc Fibrosis Transmembrane Conductance Regulator (CFTR)

Answer 4

• Membrane channel
  –  Cells that produce mucus, sweat, digesve enzymes, saliva, and tears
• Transports Cl-‐ into and out of cells
• Also regulates the funcon of other channels
  –  Ex. sodium ion channels
• CFTR
  –  member of the ABC transporter superfamily of proteins
  –  uses the energy from nucleode hydrolysis to open channel.
• See Slide 23
• side note: she’s going over the history more than i thought, might wanna look at that.

Question 5

CFTR Mutations

Answer 5

• > 1300 categorized into 4 classes:
  –  Class I-‐ defective protein product with total loss of function
  –  Class II-‐ defective protein processing leading to CFTR not in the correct Location or different from normal CFTR
  -  ∆F508 deletion ~70% of CF patients
  –  Class III-‐ defective regulation of channel opening of CFTR
  –  Class IV-‐ defective ion conduction

Question 6

Cystic Fibrosis

Answer 6

• Genetic disease
  –  Autosomal recessive disorder
  –  >1,300 mutations in the CF gene
  –  >10 million white Americans are Asymptomatic carriers
  *  Symptoms vary
  –  Very salty-‐tasting skin
  –  Persistent coughing
  –  Wheezing/ shortness of breath
  –  Excessive appetite but poor weight gain
  –  Greasy, bulky stools
• See Slide 28

Question 7

Why is the disease CF so prevalent in humans?

Answer 7

• High incidence of CF in Northern Europeans and descendants.
• Hypothesis: Heterozygotes in the Population have 50% Functional CFTRs and Selective advantage in Resisting death by cholera.