Antibiotics & Anti-fungals

Question 1

Describe the distinctive features of:

a. Gram positive bacteria
b. Gram negative bacteria
c. Mycolic bacteria

Give an example of each.

Answer 1

a. Gram positive bacteria
Thick peptidoglycan cell wall (e.g. Staphylococcus Aureus)

b. Gram negative bacteria
Outer membrane that contains lipopolysaccharide
(e.g. E. coli)

c. Mycolic bacteria
Outer mycolic acid layer
(e.g. Mycobacterium Tuberculosis)

Question 2

Describe important reactions involved in the nucleic acid synthesis process in bacteria

Answer 2

1. Paraaminobenzoate (PABA) is converted into Dihydropteroate (DHOp) - catalysed by DHOp synthase.
2. DHOp is converted into dihydrofolate (DHF).
3. DHF is converted into Tetrahydrofolate (THF) - catalysed by DHF reductase.

THF is important in DNA synthesis.

Question 3

What is DNA gyrase? What is it important in?

Answer 3

A type of topoisomerase that releases tension in DNA and is important in unwinding DNA to allow protein binding required for DNA replication

Question 4

Does bacterial RNA polymerase differ from eukaryotic RNA polymerase?

Answer 4

YES

Question 5

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

Answer 5

Eukaryote = 40S + 60S Prokaryote = 30S + 50S

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

These two drugs are sometimes used together. What is this preparation called?

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
Chloramphenicol
Aminoglycosides
Tetracyclines

Question 11

Describe how peptidoglycan is synthesised

Answer 11

• A pentapeptide is created on N-acetyl muramic acid (NAM)

* N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan

Question 12

How is the peptidoglycan is transported into the cell wall?

Answer 12

Transported across the cell membrane and into the cell wall by bactoprenol

Question 13

Describe how the peptidoglycan is incorporated into the cell wall.

Answer 13

The peptidoglycan is then incorporated into the cell wall when a transpeptidase enzyme cross-links the peptidoglycan pentapeptides

Question 14

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

Answer 14

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 15

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

Answer 15

Bacitracin – this inhibits bactoprenol

Question 16

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

Answer 16

Beta lactams – they bind covalently to transpeptidase.

Question 17

What are the three subsets of beta lactams?

Answer 17

Carbapenems
Cephalosporins
Penicillins

Question 18

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

Answer 18

Lipopeptides – disrupt Gram-positive cell membranes

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

Question 19

State the four main causes of antibiotic resistance

Answer 19

1. Unnecessary prescription
2. Antibiotic use in livestock farming
3. Lack of regulation (OTC availability)
4. Lack of development of new antibiotics

Question 20

List 5 antibiotic resistance mechanisms

Answer 20

1. Production of destruction enzymes
2. Bacteria produce another target that is unaffected by the drug
3. Alteration to the enzyme targeted by the drug (enzyme still effective but drug now ineffective)
4. Alterations in drug permeation
5. Hyperproduction of drug target

Question 21

Describe an example of (1)

Answer 21

𝛽-lactamases hydrolyse C-N bond of the 𝛽-lactam ring

Question 22

What are penicillins G and V normally used to treat?

Answer 22

Gram-positive bacteria

Question 23

Name two drugs that are relatively beta lactamase resistant.

Answer 23

Flucloxacillin and temocillin

Question 24

Name a broad-spectrum antibiotic that must be administered with another drug to become resistant to beta lactamases. What is this other drug?

Answer 24

Amoxicillin (no antibiotic resistance on its own)

Administered with Clavulanic acid

Question 25

Describe an example of (2)

Answer 25

E Coli produce different DHF reductase enzyme making them resistant to trimethoprim

Question 26

Describe an example of (3)

Answer 26

S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones

Question 27

Describe an example of (4)

Answer 27

Reductions in aquaporins & increased efflux systems; primarily of importance in gram –ve bacteria

Question 28

Describe an example of (5)

Answer 28

E Coli produce additional DHF reductase enzymes making trimethoprim less effective

Question 29

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

Answer 29

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

Question 30

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

Answer 30

Azoles (fluconazole)

Polyenes (amphotericin)

Question 31

Describe the mechanism of action of azoles. What is the example drug used to treat?

Answer 31

They inhibit CYP51p (enzyme of the CYP450 system), which is involved in membrane ergosterol synthesis.
e.g. Fluconazole (oral) treats candidiasis & systemic infections

Question 32

Describe the mechanism of action of polyenes. What is the example drug used to treat?

Answer 32

These interact with membrane ergosterols forming membrane channels (punching holes in the membrane)
e.g. Amphotericin treats systemic infections