Antibiotics

Question 1

What is an antibiotic?

Answer 1

Originally an antibiotic was defined as a substance produced by one microorganism, in low concentrations which can inhibit the growth of other microorganisms. But now synthetic, semi-synthetic antibiotics can also be included in the definition.

Question 2

Antibacterial agents (antibiotics administered to inhibit growth of bacteria) have 5 mechanisms of action. What are these 5 mechanisms?

Answer 2

1. Inhibition of cell wall synthesis
2. Inhibition of protein synthesis
3. Inhibition of nucleic acid synthesis
4. Production of anti-metabolic agents
5. Inhibitors of the cytoplasmic membrane function/membrane disruption

Question 3

Name the antibiotic inhibitors for cell wall synthesis.

Answer 3

Beta-lactams

Question 4

Penicillin affects cell wall synthesis. Explain how this occurs. Hint: Transpeptidase.

Answer 4

Transpeptidase is an enzyme required to form crosslinks of peptide chains between the adjacent sides of peptidoglycan.
Penicillin inhibits enzyme as it mimics the terminus of transpeptidase. Causes bacteria to produce leaky cell walls.
Also inactivates the natural inhibitor for autolytic enzymes - causes further destruction of cell wall and death.

Question 5

Name 4 members of Beta-Lactam family - they have the same Beta-lactam nucleus.

Answer 5

Penicillins
Monobactams
Cephalosporins
Cephamycins

Question 6

Describe how antimetabolic agents affects bacteria - Folate synthesis.

Answer 6

These inhibit bacterial metabolic pathways which produce precursors for nucleic acid synthesis.
Commonly, sulfonamides and trimethoprim are created.
These disrupt biosynthesis of purines and pyrimidines from PABA and glutamate.
Interferes with Krebs cycle.

Question 7

Name the 3 inhibitors of protein synthesis.

Answer 7

Aminoglycosides
Tetracyclines
Macrolides

Question 8

Describe 2 ways in which aminoglycosides work.

Answer 8

1. Inhibition of protein synthesis by freezing the initiation complex (The 70S subunit).
2. Misreading codons via distortion of A site on ribosome.

Question 9

Outline the mechanism of how tetracyclines work.

Answer 9

Tetracyclines inhibit protein synthesis by binding to the 30S ribosome subunit, preventing access of aminoacyl tRNA to the acceptor site (A site) on mRNA-ribosome complex.

Question 10

How do macrolides work?

Answer 10

These are bacteriostatic agents, which inhibit protein synthesis by binding reversibly to the 50S ribosome subunit.

Question 11

Name 3 agents which are inhibitors of nucleic acid synthesis.

Answer 11

Nitrofurans
Rifampicin
Quinolones

Question 12

What is the function of bacterial gyrase?

Answer 12

Bacterial DNA gyrase is responsible for the introduction of negative supercoils to counter the introduction of positive supercoils in the DNA double helix.
Retains the structural integrity of the double helix DNA.

Question 13

How do quinolones work to inhibit nucleic acid synthesis?

Answer 13

Quinolones target bacterial DNA gyrase and topoisomerase IV.

Question 14

Outline the mechanism by which Rifampicin works.

Answer 14

Rifampicin inhibits DNA-dependent RNA polymerase thus preventing transcription of RNA from the DNA template. Overall inhibits synthesis of nucleic acids.

Question 15

What are drugs of last course?

Answer 15

These are reserved drugs according to antimicrobial stewardship. Reserved drugs are restricted in use to prevent the emergence of resistance.