Antibiotics and Anti-fungals

Question 1

Describe the distinctive features of: a. Gram positive bacteria b. Gram negative bacteria c. Mycolic bacteria

Answer 1

a. Gram positive bacteria

• Thick peptidoglycan cell wall
• E.g. Staphylococcus Aureus

b. Gram negative bacteria

• Outer membrane that contains lipopolysaccharide (LPS)
• E.g. Escherichia Coli

c. Mycolic bacteria

• Same as gram positive
• but with an additional outer mycolic acid layer
• E.g. Mycobacterium Tuberculosis

Question 2

State the steps involved in the production of THF from PABA.

Answer 2

PABA –> DHOp (enzyme = dihydropterase synthase) DHOp –> DHF DHF –> THF (enzyme = DHF reductase)

Question 3

What is DNA gyrase?

Answer 3

A type of topoisomerase (topoisomerase II) It releases tension in DNA and is important in unwinding DNA to allow protein binding required for DNA replication

Question 4

What does RNA polymerase do?

Answer 4

Produces RNA from a DNA template

Question 5

What is the key difference between ribosomes in eukaryotes and prokaryotes?

Answer 5

Eukaryote: 40S + 60S = 80s Prokaryote: 30S + 50S = 70s

Question 6

State two classes of drugs that interfere with nucleic acid synthesis and name the enzymes that they inhibit.

Answer 6

• Sulphonamides – inhibits dihydropterate synthase
• Trimethoprim – inhibits DHF reductase

Question 7

What is the name of the preparation containing the 2 drugs that interfere with nucleic acid synthesis?

Answer 7

Co-trimoxazole

Question 8

Name a group of drugs that interfere with DNA replication and state its targets.

Answer 8

Fluoroquinolones (e.g. ciprofloxacin) Inhibits bacterial DNA gyrase and topoisomerase IV

Question 9

Name a group of drugs that interfere with RNA synthesis and state its main target.

Answer 9

Rifamycins (e.g. rifampicin) Inhibits RNA polymerase

Question 10

List 4 groups of drugs that interfere with ribosomes.

Answer 10

Macrolides e.g. Erythromycin Chloramphenicol Aminoglycosides e.g. Gentamicin Tetracyclines

Question 11

Describe how peptidoglycan is synthesized, transported to the cell wall and incorporated into the cell wall.

Answer 11

In the cytoplasm:

• A pentapeptide is created on N-acetyl muramic acid (NAM)
• N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan
• Peptidoglycan is then transported across the cell membrane into the periplasm by bactoprenol
• The peptidoglycan is then incorporated into the cell wall by transpeptidase enzyme, which cross-links the peptidoglycan pentapeptides

Question 12

Which groups of drugs interfere with peptidoglycan synthesis and how do they do this?

Answer 12

1. Glycopeptides (e.g. vancomycin)

• They bind to the pentapeptides and inhibit peptidoglycan synthesis
• This is used as a last resort for Gram-positive bacteria that are resistant to other antibiotics

Question 13

Name a drug that interferes with peptidoglycan transport and state its target.

Answer 13

Bacitracin – this inhibits bactoprenol, hence preventing peptidoglycan transport

Question 14

Name a class of drugs that inhibit peptidoglycan incorporation and explain how they do this.

Answer 14

Beta lactams – they bind covalently to transpeptidase, which inhibits peptidoglycan incorporation into the cell wall

Question 15

What are the three subsets of beta lactams?

Answer 15

Carbapenems Cephalosporins Penicillins

Question 16

Name two drugs that interfere with cell membrane stability and explain how they do this.

Answer 16

• Lipopeptides – disrupt Gram-positive cell membranes
• Polymyxins – bind to lipopolysaccharide and disrupt Gram-negative cell membranes

Question 17

List five mechanisms of antibiotic resistance and give a brief description of each.

Answer 17

Additional target– the bacteria produce another target that is unaffected by the drug e.g. different DHF reductase enzyme Hyperproduction – the bacteria increase the production of the target so the antibiotics are less effective (this is energy inefficient) e.g. over-prodution of DHF reductase Altered target site – there is an alteration in the drug target so that the drug is no longer effective e.g. mutations in DNA gyrase Alteration in drug permeation– down regulation of aquaporins (responsible for allowing drugs into cells) or the upregulation of efflux systems Production of destruction enzymes– beta-lactamases hydrolyse the C-N bond in the beta-lactam ring rendering the beta-lactams inactive

Question 18

What are the four types of fungal infection, characterised based on the tissues/organs affected?

Answer 18

Superficial – outermost layers of skin Dermatophyte – skin, hair or nails Subcutaneous – innermost skin layers Systemic – primarily respiratory tract

Question 19

What are the two main groups of anti-fungals? Give an example of each.

Answer 19

Azoles (fluconazole) Polyenes (amphotericin)

Question 20

Describe the mechanism of action of azoles.

Answer 20

They inhibit a CYP450 dependent enzyme which is involved in ergosterol production (a membrane sterol of fungi)

Question 21

Describe the mechanism of action of polyenes.

Answer 21

These interact with ergosterol (a membrane sterol) and form channels (punching holes in the membrane)

Question 22

What is important for prokaryotic DNA synthesis?

Answer 22

Tetrahydrofolate (THF) Produced in a synthesis pathway starting with Dihydropteroate (DHOp)