ALT Antifungal targets and mechanisms of acquired antifungal resistance. The triazoles and echinocandins target fungal enzymes Erg11 and Fks1, respectively. Mutations in these drug targets promote resistance. Mutations leading to the upregulation of efflux pumps also contribute to triazole resistance. Antifungal activity driven by polyenes is driven by binding ergosterol in the cell membrane. Mutations in ergosterol biosynthetic pathway genes such as ERG6 and ERG3 limit ergosterol accumulation in the membrane, rendering polyenes inactive against resistant mutants. Pyrimidine analogs, such as flucytosine, are metabolized into nucleotoxic downstream analogs. Loss of function of any of the genes responsible for this metabolism, such as FUR1, FCY1, or FCY2, ablates the antifungal activity of these compounds.