Table 2: Resistance mechanisms of major systemic antifungal drugs. Antifungal resistance is based on different mechanisms, namely, (i) reduced drug intracellular accumulation, (ii) decreased target affinity/processivity for the drug, and (iii) counteraction of the drug effect.

Antifungal classGenetic basis for resistanceFunctional basis for resistance

AzolesUpregulation of CDR1/CDR2 and MDR1 by point mutations in TAC1 and MRR1 transcription factors(i) Upregulation of drug transporters
Point mutations in ERG11 (ii) Decreased lanosterol 14-α-demethylase binding affinity for the drug
Upregulation of ERG11 by gene duplication and transcription factor regulation(iii) Increased concentration of lanosterol 14-α-demethylase
Point mutations in ERG3 (iii) Inactivation of C5 sterol desaturase leading to alterations in the ergosterol synthetic pathway

EchinocandinsPoint mutations in FKS1 and FKS2 (ii) Decreased glucan synthase processivity for the drug

PolyenesPoint mutations in ERG3 and ERG6 (iii) Decreased ergosterol content in cells

Nucleoside analoguesPoint mutations in FCY2 (i) Inactivation of cytosine permease affecting drug uptake
Point mutations in FCY1 (iii) Inactivation of cytosine deaminase leading to alterations in the metabolism of 5-fluorocytosine
Point mutations in FUR1 (iii) Inactivation of uracil phosphoribosyl transferase leading to alterations in the metabolism of 5-fluorocytosine