Lecture 21

Question 1

Malaria

Answer 1

• Caused by protozoan parasite, Plasmodium sp.
• Transmission by Anopheles sp. mosquitoes
• Fevers, chills, anemia due to loss of red blood cells

Question 2

Life cycle

Answer 2

• Parasite sucked up -> oocysts develop in gut wall -> sporozoites develop in oocyst -> sporozoites migrate to salivary glands -> sporozoites injected with mosquito bite -> gametocytes

Question 3

Methods of control

Answer 3

• Killing the parasite (drug treatments in humans)
• Killing the vector (mosquito control)
• Decreasing contact between humans and vector

Question 4

Targeting parasites through drug treatment

Answer 4

• Leads to drug resistance in parasites
• Why?
  
  • There is genetic variation in parasite sensitivity to drugs
  • Under pressure, less sensitive strains survive better, and competitors have been removed

Question 5

Targeting mosquitoes with insecticides

Answer 5

• Leads to insecticide resistance in mosquitoes

Question 6

Challenges for malaria control

Answer 6

• Evolution of parasite
• Evolution of mosquito
• Ecological factors

Question 7

Antibiotics and bacterial pathogens

Answer 7

• Antibiotics kill bacteria by disrupting a variety of biochemical processes
• Major force of selection for bacteria
  
  • Susceptible genotypes are killed by antibiotics
  • Resistant genotypes survive
• Antibiotic use leads to a selection experiment
• Antibiotic resistance evolves rapidly
• Resistance increases with antibiotic use
• Resistance decreases with decreased drug use

Question 8

Evolution of antibiotic resistance

Answer 8

• Use of antibiotics creates a strong selective environment favoring evolution of antibiotic resistance
• Sorting resistant from susceptible genotypes (drugs increase relative fitness of any existing resistant types)
• Mutation from susceptible to resistant genotypes facilitated by high replication rates

Question 9

Plasmids and Horizontal Gene Transfer

Answer 9

• Resistance genes can be transferred among bacterial cells via extra-chromosomal loops of DNA called plasmids

Question 10

HGT, off-target selection and resistance evolution

Answer 10

• Use of antibiotics creates a strong selective environment favoring evolution of antibiotic resistance, even among commensal bacteria
• Use of antibiotics for non-bacterial infections can exacerbate this problem through HGT of resistance genes
• Use of antibiotics in agriculture further exacerbates this problem

Question 11

Life Cycle of HIV

Answer 11

• HIV is a dsRNA retrovirus
• Infects host CD4+ helper T cells
• Viral enzyme (reverse transcriptase) turns RNA to DNA
• Embeds its genome into host DNA
• Viral genes transcribed and translated by host machinery
• New virus buds out of host cells

Question 12

AZT resistance in HIV

Answer 12

• Azidothymidine
• Drug (AZT) was developed in early 1980s
• Binds to and inactivates an HIV enzyme that is required for viral replication
• New mutant enzyme arose with altered binding site that was resistant to AZT
• Appearance and spread of mutant enzymes have been documented repeatedly

Question 13

Why does HIV evolve so fast

Answer 13

• Massive population size (10^10 new virions/day)
• Short generation time (1 year = 300 viral generations)
• High mutation rate (20-50% errors/replication)
• Resistant mutation is likely generated quickly

Question 14

Possible solutions

Answer 14

• Bigger doses of drugs
• Earlier treatment
• Combinations of drugs

Question 15

Other ways forward

Answer 15

• Reduce unnecessary drug use
• Slow spread of infection thus reducing drug use
• Identify other ways of treating infections (novel therapeutics, new ways of using old drugs)

Question 16

Drug treatment

Answer 16

• Generates strong direct fitness advantage to any resistant strains and an indirect fitness advantage through deaths of competitors