Antifungals Flashcards
what makes fungal cells different from other eukaryotes
cell wall that contains chitin and glucan
cell membrane that contains ergosterol
what is the function of flucytosine
inhibition of nucleic acid synthesis
function of sordarins and azasordarins
inhibition of protein synthesis
function of griseofulvin
disruption of microtubules and inhibition of mitosis
how do most antifungals act
by targeting the cell wall to inhibit glucan synthesis or disruption of the cell membrane by inhibiting ergosterol synthesis
what is the structure of fungal cell walls
inner layer - glucans and chitin
outer layer - mannosew
what are echinocandins and their mechanism of action
beta-1,3-glucan synthesis inhibitors
act by targeting FKS1p subunit via non-competitive inhibition
what is a chitin synthesis inhibitor
nikkomycin z
via competitive inhibition
what is the function of ergosterol
basically the fungi version of cholesterol
what targets ergosterol synthesis
polyenes:
amphotericin B
nystatin
what is the potential mechanism of action of polyenes
may act as ionophores - creation of a pore that effluxes K+/H+
what is the selective toxicity of polyenes
they a have a low affinity for cholesterol
causes vomiting/fever/anaphylaxis/nephrotoxicity
how do allylamines inhibit ergosterol synthesis
inhibit squalene epoxidase
how do azoles/triazoles inhibit ergosterol synthesis
by inhibiting lanosterol-alpha-14 demethylase
via competitive inhibition
what is griseofulvin and what does it bind to
an antimitotic
inhibits tubulin/spindle formation/mitosis
binds to keratin
how can fungi develop resistance to azoles
reduced binding affinity - mutation in L98H enzyme
overexpression of drug target
hypermutations
chromosomal changes
how is resistance developed for echinocandins
mutation in FKS1
cell wall stress pathway involving unfolded protein response
how do fungal cells confer resistance to polyenes
reduce or increase synthesis of ergosterol
cell membrane stress leads to release of cell stress responders
how do fungi confer resistance to flucytosine
cytosone permease reduces uptake of flucytosine
5-FU/5-FUMP point mutations to reduce their binding affinity
what is the purpose of genetic screening of fungal cells
identifying essential fungi genes that can be targeted
