Targeting Pathogenic Organisms: Fungi Flashcards
Why are fungi harder to treat than bacteria
They have more similarities to humans than bacteria as they are also eukaryotes.
What are the 5 antifungal targets and an example for each?
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
What is the component of fungal cell membranes?
Ergosterol. Cholesterol in humans.
Polyene structure
polyol domain, polyene domain, sterol A binding domain
MOA polyene
the sterol A binding domain binds to the ergosterol in cell membranes allowing polyene insertion, causing leakage of intracellular ions and cell death
Polyene MOA is similar to
Polymyxin
Example of polyene
Amphotericin B
Example of azole
fluconazole
azole structure
5 membered heterocyclic compound, Nitrogen atom and one other non-carbon atom.
MOA azole
inhibit the lanosterol 14-alpha demethylase enzyme which is involved in ergosterol synthesis -> causes depletion of ergosterol -> toxic sterols accumulate -> cell death.
MOA of 5FC
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.
what does 5FU compete with
Uracil.
is 5FU phosphorylated or does it phosphorylate thymidylate synthase
5FU is phosphorylated and so binds covalently to thymidylate synthase.
are there vaccines for fungi
no.
what is the fungal cell wall made of
Chitin and glucan fibrils
MOA echinocandins
inhibit the beta-glucan synthase enzyme preventing beta-glucan synthesis and cell wall lysis
what is griseofulvin a metabolite of
Penicillum griseofulvin and penicillum janczewskii.
what subunits position the centrosome
alpha and beta tubulin subunits
MOA griseofulvin
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.
