Module 4: Section 3B

Question 1

Charles Darwin mutation theory

Answer 1

• Believed in random mutation theory
• Changes in traits were random and if a trait is not beneficial, it is not retained in the population
• Natural selection

Question 2

Jean-Baptiste Lamarck

Answer 2

• Physiological adaptation theory
• Believed that change is driven by what organisms want or need
• Ex: Giraffes grew long necks from stretching to reach tree food

Question 3

Replica plating experiment

Answer 3

• In 1950s Joshua and Ester Lederberg devised an experiment to test the 2 theories
• Uses a phage that infected E.coli

Question 4

Replica plating experiment - procedure

Answer 4

• Bacteria is grown over 3 days
• Bacteria are replated daily onto phage plates, and only mutants resistant to the bacteriophage form colonies

Question 5

Outcome of replica plating for Darwin’s theory

Answer 5

• If mutations happen spontaneously, early plates have the fewest mutants
• but they appear in the same spots on later replica plates
• Darwin’s theory was proven to be correct

Question 6

Outcome of replica plating for Lamarck’s theory

Answer 6

Each mutation would occur in a different location and not accumulate over time

Question 7

Reason 1 ribosomes are a good target for antibiotics

Answer 7

• Protein synthesis is an essential process
• If inhibited cells stop dividing and/or die

Question 8

Reason 2 ribosomes are a good target for antibiotics

Answer 8

• Bacterial protein synthesis involves different ribosomal structures than eukaryotes
• Antibiotics targeting unique bacterial ribosomes will not harm the host

Question 9

Reason 3 ribosomes are a good target for antibiotics

Answer 9

Combination of antibiotics targeting different stages of protein synthesis can be used to help top prevent development of antibiotic resistance

Question 10

Where do most ribosome targeting antibiotics interfere with the cell?

Answer 10

With the elongation step in protein synthesis

Question 11

When targeting 30S subunit:

Answer 11

Antibiotic interaction sites are clustered along the path of the mRNA and tRNA interactions

Question 12

When targeting 50S subunit:

Answer 12

• Antibiotic interaction sites cluster at or near the peptidyl-transferase centre (PTC)
• PTC is where peptide-bond formation occurs

Question 13

Streptomycin and tetracycline

Answer 13

Interfere with the delivery of tRNAs to the A-site

Question 14

PTC-targeting antibiotics

Answer 14

• Inhibit peptide-bond formation by perturbing or preventing the correct position of aminoacylated ends of tRNAs in the PTC
• Ex: Chloramphenicol and clindamycin

Question 15

Aminoglycosides

Answer 15

Interfere with peptide elongation which results in misreading of the mRNA and truncated proteins

Question 16

Puromycin

Answer 16

Termination is inhibited by peptidyl-transferase inhibitors

Question 17

Mechanisms of bacterial resistance to antibiotics - 1

Answer 17

Impaired drug influx owing to law of membrane permeability

Question 18

Mechanisms of bacterial resistance to antibiotics - 2

Answer 18

Active efflux of the drug from the cell

Question 19

Mechanisms of bacterial resistance to antibiotics - 3

Answer 19

Mutation of ribosome (without affecting function)

Question 20

Mechanisms of bacterial resistance to antibiotics - 4

Answer 20

• Modification of the target (ribosomal RNA or ribosomal proteins)
• Lowers affinity of the drug for the target

Question 21

Mechanisms of bacterial resistance to antibiotics - 5

Answer 21

• Overproduction of a molecule that mimics the target that lowers the effective drug concentration
• Target remains unbound

Question 22

Mechanisms of bacterial resistance to antibiotics - 6

Answer 22

Recruitment of a specialized protein factor to actively remove the drug from the target

Question 23

Mechanisms of bacterial resistance to antibiotics - 7

Answer 23

Modification of the drug

Question 24

Mechanisms of bacterial resistance to antibiotics - 8

Answer 24

Degradation of the drug

Question 25

2 criteria for beneficial mutations

Answer 25

1. the mutation gives the bacteria resistance to the antibiotic 2. The mutation does not affect the normal functions of the cell

Question 26

How Streptomycin Works

Answer 26

- Streptomycin binds to the 30S ribosomal subunit and distorts the tRNA binding site - Blocks normal translation

Question 27

How Bacteria Become Resistant to Streptomycin

Answer 27

- A point mutation in the 30S subunit alters the streptomycin binding site - Gives resistance without affecting ribosome function

Question 28

Reasons Certain Bacteria Are High-Risk for Antibiotic Resistance

Answer 28

- Severity of the infections they cause - Whether treatment requires long hospital stays - How common antibiotic resistance is in community-acquired infections - How easily they spread - Whether or not they can be prevented - The extend of treatment options remaining - If new antibiotics to treat them are already in the R&D pipeline

Question 29

How does antibiotic resistance spread between bacteria?

Answer 29

- once a helpful mutation occurs, bacteria can share resistance genes through horizontal gene transfer - Allows many resistance genes to build up in one species

Question 30

Why is HIV prone to developing drug resistance?

Answer 30

HIV’s genome mutates quickly, so after exposure to antiretroviral drugs, it can accumulate mutations that let it keep replicating despite treatment

Question 31

What is the most effective treatment approach for HIV?

Answer 31

- A combination of several drugs at high doses targets multiple stages of the viral life cycle - Reduces viral load to undetectable levels