Lecture 21: Antifungals

Question 1

Where are fungal locations usually located?

Answer 1

Often superficial

If systemic = life threatening

Question 2

Composition of the cell wall of fungi? Cell membrane?

Answer 2

Cell wall: Chitin (Polymer of N-acetylglucosamine)

Cell membrane: contains ergosterol

Question 3

Can you treat fungi with antibiotics?

Answer 3

No, they are resistant to antibiotics

Question 4

What is linked to increased incidence in fungal infections?

Answer 4

Suppressed immune systems

Long term antibiotic treatment

Question 5

Mechanism of amphotericin B - anti fungal

Answer 5

Binds to ergosterol (not cholesterol).

Forms pores.

Potassium and other small molecules are lost through the pore, causing cell death

Question 6

Mechanism of flucytosine - antifungal

Answer 6

Enters via specific cytosine permease (not in mammals).

Converted to 5’ fluorodeoxyuridine monophosphate (5 FdUMP).

Flase nucleotide inhibits thymidylate synthase. Blocks thymidylic acid (needed for DNA).

Question 7

Mechanism of azoles - antifungals

Answer 7

Synthetic triazole.

Inhibits C-14 alpha-demethylase (cyt P450 enzyme).

Blocks demethylation of lanosterol to ergosterol.

Disrupts membrane structure/function

Question 8

Mechanism of echinocandin - antifungals

Answer 8

Inhibits beta-(1,3)-D-glycan.

Cell disruption and death.

Question 9

Mechanism of terbinafine - anti fungal

Answer 9

Squalene epoxidase usually converts squalene to ergosterol

Terbinafine inhibits squalene epoxidase and blocks ergosterol.

Squalene build up is toxic