Figure 1.

Mechanisms of antifungal agent resistance. Polyenes (A) and azoles (B) are membrane targeting antifungal drugs while echinocandins are cell wall-active agents. (A) Polyene resistance is often attributed to loss-of-function mutations in ergosterol biosynthetic genes which lead to depletion of ergosterol, the fungi-specific cell membrane sterol. Resistance mechanisms for Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus are outlined in dashes. (B) Azole resistance can result from the upregulation of two classes of efflux pumps that remove the drug from the cell; through the mutation or overexpression of ERG11, which minimizes the impact of the drug on the target; or alterations in ergosterol biosynthesis, such as the loss-of-function mutation of ERG3, which blocks the accumulation of a toxic sterol intermediate that is produced when ERG11 is inhibited. (C) Resistance to echinocandins can result from mutations in FKS1 that minimize the impact of the drug on the target.