Antifungals

Question 1

what makes fungal cells different from other eukaryotes

Answer 1

cell wall that contains chitin and glucan
cell membrane that contains ergosterol

Question 2

what is the function of flucytosine

Answer 2

inhibition of nucleic acid synthesis

Question 3

function of sordarins and azasordarins

Answer 3

inhibition of protein synthesis

Question 4

function of griseofulvin

Answer 4

disruption of microtubules and inhibition of mitosis

Question 5

how do most antifungals act

Answer 5

by targeting the cell wall to inhibit glucan synthesis or disruption of the cell membrane by inhibiting ergosterol synthesis

Question 6

what is the structure of fungal cell walls

Answer 6

inner layer - glucans and chitin
outer layer - mannosew

Question 7

what are echinocandins and their mechanism of action

Answer 7

beta-1,3-glucan synthesis inhibitors
act by targeting FKS1p subunit via non-competitive inhibition

Question 8

what is a chitin synthesis inhibitor

Answer 8

nikkomycin z
via competitive inhibition

Question 9

what is the function of ergosterol

Answer 9

basically the fungi version of cholesterol

Question 10

what targets ergosterol synthesis

Answer 10

polyenes:
amphotericin B
nystatin

Question 11

what is the potential mechanism of action of polyenes

Answer 11

may act as ionophores - creation of a pore that effluxes K+/H+

Question 12

what is the selective toxicity of polyenes

Answer 12

they a have a low affinity for cholesterol
causes vomiting/fever/anaphylaxis/nephrotoxicity

Question 13

how do allylamines inhibit ergosterol synthesis

Answer 13

inhibit squalene epoxidase

Question 14

how do azoles/triazoles inhibit ergosterol synthesis

Answer 14

by inhibiting lanosterol-alpha-14 demethylase
via competitive inhibition

Question 15

what is griseofulvin and what does it bind to

Answer 15

an antimitotic
inhibits tubulin/spindle formation/mitosis
binds to keratin

Question 16

how can fungi develop resistance to azoles

Answer 16

reduced binding affinity - mutation in L98H enzyme
overexpression of drug target
hypermutations
chromosomal changes

Question 17

how is resistance developed for echinocandins

Answer 17

mutation in FKS1
cell wall stress pathway involving unfolded protein response

Question 18

how do fungal cells confer resistance to polyenes

Answer 18

reduce or increase synthesis of ergosterol
cell membrane stress leads to release of cell stress responders

Question 19

how do fungi confer resistance to flucytosine

Answer 19

cytosone permease reduces uptake of flucytosine
5-FU/5-FUMP point mutations to reduce their binding affinity

Question 20

what is the purpose of genetic screening of fungal cells

Answer 20

identifying essential fungi genes that can be targeted