Figure 1.

Mechanisms of resistance to antifungal drugs that target the cell membrane—the azoles and polyenes. (A) Azole resistance can emerge through multiple mechanisms including overexpression or alteration of the drug target, up-regulation of drug transporters, or cellular changes that reduce drug toxicity or enable tolerance of drug-induced stress. The colored circles indicate ergosterol biosynthesis intermediates. (B) Polyene resistance generally involves depletion of the target ergosterol attributable to loss-of-function mutations in ergosterol biosynthetic genes. Bullet points describe resistance mechanisms for Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. Dimmed images represent mechanisms that do not play a key role in resistance to the indicated drug class. (From Cowen 2008; adapted, with permission, from Macmillan © 2008.)