Antibiotic and anti fungal drugs

Question 1

Recall the differences between gram positive and gram negative bacteria and give an example of each

Answer 1

Gram-positive: thick peptidoglycan layer e.g. Staphylococcus aureus
Gram-negative: two cell membranes, outer membrane contains lipopolysaccharide e.g. E. Coli

Question 2

What is the other type of bacteria other than gram -/+ bacteria?

Answer 2

Mycolic bacteria
Outer mycolic acid layer
e.g. mycobacterium tuberculosis

Question 3

Describe nucleic acid synthesis in bacteria

Answer 3

PABA (proaminobenzoate) converted by DHOp synthase to Dihydropterate.
Dihydropterate is converted to Dihydrofolate.
Dihydrofolate converted by DHF reductase into Tetrahydrofolate (THF).
THF is essential for DNA synthesis.

Question 4

What is needed for DNA replication in bacteria?

Answer 4

DNA gyrate (Type II topoisomerase) releases tension in dsDNA to allow the DNA to unwind for replication

Question 5

What is needed for RNA synthesis in bacteria?

Answer 5

RNA polymerase to produce RNA from DNA template.

[This differs to the eukaryotic RNA polymerase.]

Question 6

What is needed for protein synthesis in bacteria?

Answer 6

Ribosomes are required to produce proteins from RNA templates

Question 7

What are the drugs used to target DNA synthesis in bacteria?

Answer 7

• Sulphonamides inhibit DHOp synthase

- Trimethoprim inhibits DHF reductase (so THF cannot be produced)

Question 8

What are the drugs used to target DNA replication in bacteria?

Answer 8

Fluoroquinolones (e.g. Ciprofloxacin) inhibit DNA gyrase & topoisomerase IV

Question 9

What are the drugs used to target RNA synthesis in bacteria?

Answer 9

The rifamycins (e.g. Rifampicin) inhibits bacterial RNA polymerase

Question 10

What are the drugs used to target protein synthesis in bacteria?

Answer 10

Inhibited by:
Aminoglycosides (e.g. Gentamicin)
Chloramphenicol
*Macrolides (e.g. Erythromycin)
Tetracyclines

Question 11

Describe the three steps involved in bacterial cell wall synthesis

Answer 11

1. Peptidoglycan synthesis; A pentapeptide is created on N-acteyl muramic acid (NAM)
   NAM joins with NAG to form peptidoglycan
2. Peptidoglycan transportation; Ptg is transported across the membrane by bactoprenol
3. Peptidoglycan integration; Ptg pentapeptides cross-links with transpeptidase enzymes

Question 12

What is the drug that targets Peptidoglycan synthesis?

Answer 12

Glycopeptides (e.g. vancomycin) bind to pentapeptide

Question 13

What is the drug that targets Peptidoglycan transportation?

Answer 13

Bacitran inhibits bactoprenol regeneration

Question 14

What is the drug that targets Peptidoglycan integration?

Answer 14

Beta-lactams bind covalently to transpeptidase, they include;

• Carbapenems
• Cephalosporins
• Penicillins

Question 15

What is the drug that targets cell wall stability?

Answer 15

Target gram +: Lipoproteins disrupt the cell walls

Target gram -: Polymyxins binds to LPS and disrupt the cell membranes

Question 16

Name the five main methods of antibiotic resistance

Answer 16

1. Produce alternate target; different DHF reductase produced
2. Hyperproduction; overproduction of DHF reductase
3. Drug permeation; decreased drug influx, increased drug efflux
4. Enzyme alteration; mutations in DNA gyrase enzyme
5. Production of destruction enzymes; production of beta-lactamase enzyme

Question 17

Give examples of drugs which are resistant to beta-lactamase

Answer 17

Flucloxacillin + Temocillin - betalactamase resistant

Amoxicillin - Gram -ve bacteria, not resistant on its own but Clavulanic acid is co-administered

Question 18

What are the different layers of tissue that fungal infections can infect?

Answer 18

Superficial: outermost layer of skin
Dermatophyte: skin, hair, nails
Subcutaneous: innermost layer of skin
Systemic: primarily affects respiratory tract

Question 19

What are the two anti-fungal drug classes, how do they work and give an example

Answer 19

Azoles e.g. fluconazole, ketoconazole; inhibit CYP450 enzymes needed for synthesis of ergosterol.

Polyenes e.g. amphotericin; interact with cell membrane sterols forming membrane channels. Can be given IV in systemic infections.

Question 20

What is the cell membrane synthesis in a fungal cell?

Answer 20

Lanosterol via Cyp51p -> Ergosterol