Targeting Pathogenic Organisms: Fungi

Question 1

Why are fungi harder to treat than bacteria

Answer 1

They have more similarities to humans than bacteria as they are also eukaryotes.

Question 2

What are the 5 antifungal targets and an example for each?

Answer 2

1) Direct cell membrane interaction: Polyene
2) Disruption of cell membrane synthesis: Azole
3) Cell wall: Echinocandin
4) DNA/RNA synthesis: 5FC
5) Microtubule: Griseofulvin

Question 3

What is the component of fungal cell membranes?

Answer 3

Ergosterol. Cholesterol in humans.

Question 4

Polyene structure

Answer 4

polyol domain, polyene domain, sterol A binding domain

Question 5

MOA polyene

Answer 5

the sterol A binding domain binds to the ergosterol in cell membranes allowing polyene insertion, causing leakage of intracellular ions and cell death

Question 6

Polyene MOA is similar to

Answer 6

Polymyxin

Question 7

Example of polyene

Answer 7

Amphotericin B

Question 8

Example of azole

Answer 8

fluconazole

Question 9

azole structure

Answer 9

5 membered heterocyclic compound, Nitrogen atom and one other non-carbon atom.

Question 10

MOA azole

Answer 10

inhibit the lanosterol 14-alpha demethylase enzyme which is involved in ergosterol synthesis -> causes depletion of ergosterol -> toxic sterols accumulate -> cell death.

Question 11

MOA of 5FC

Answer 11

5FC is inactive in itself but when transported by cytosine permease present in fungal cells it becomes activated to 5FU which is highly toxic to mammalian cells as it incorporates into RNA by competing with uracil. 5FU is also phosphorylated and binds to the thymidylate synthase enzyme covalently which causes DNA damage.

Question 12

what does 5FU compete with

Answer 12

Uracil.

Question 13

is 5FU phosphorylated or does it phosphorylate thymidylate synthase

Answer 13

5FU is phosphorylated and so binds covalently to thymidylate synthase.

Question 14

are there vaccines for fungi

Answer 14

no.

Question 15

what is the fungal cell wall made of

Answer 15

Chitin and glucan fibrils

Question 16

MOA echinocandins

Answer 16

inhibit the beta-glucan synthase enzyme preventing beta-glucan synthesis and cell wall lysis

Question 17

what is griseofulvin a metabolite of

Answer 17

Penicillum griseofulvin and penicillum janczewskii.

Question 18

what subunits position the centrosome

Answer 18

alpha and beta tubulin subunits

Question 19

MOA griseofulvin

Answer 19

It binds to and disrupts both the α and β tubulin subunits which position centrosomes → Prevents spindle formation and mitosis in fungi → Prevent fungi from dividing.