How is flucytosine selectively activated inside fungal cells?

Flucytosine spontaneously converts to a nucleotide analog in serum, and this active form selectively binds fungal rRNA because fungal ribosomes have an extra protein subunit not present in human ribosomes.

Fungal cells have a cytosine deaminase that converts flucytosine to 5-fluorouracil (5-FU), generating toxic metabolites that interfere with DNA/RNA synthesis; human cells lack this activating enzyme.

Human cells activate flucytosine into a harmless metabolite by methylation, whereas fungal cells acetylate flucytosine into a toxic metabolite, producing selective toxicity.

Flucytosine is conjugated to ergosterol in fungal membranes, a reaction that does not occur in human cells because human membranes contain cholesterol instead of ergosterol.