Fig. 4
From: Cryptococcus neoformans, a global threat to human health
Antifungals, targets, and antifungal resistance mechanism. Three main classes of drugs are used in the treatment of cryptococcal infections: polyenes (AmB), azoles (fluconazole), flucytosine. C. neoformans is intrinsic resistant to echinocandins (shown in dotted lines). AmB binds to ergosterol in the cell membrane, which forming pores and exerting fungicidal activity. Fluconazole targets the ergosterol biosynthetic enzyme Erg11. Flucytosine blocks DNA synthesis. C. neoformans cells develop resistance to different drugs through different mechanisms. The exact mechanism leading to AmB resistance is not yet clear. Fluconazole resistance has been reported to be associated with aneuploidy, heteroresistance and mutations in the ERG11 gene. Flucytosine resistance may be associated with mutations in genes related to flucytosine conversion, hypermutation, and transposon mutagenesis. The echinocandins resistance is attributed to the interaction of Cdc50 and Crm1, and preventing drug uptake could also arise echinocandins resistance