Antifungal Resistance and New Strategies to Control Fungal Infections

Table 2

Nature, target, mode of action, and fungal resistance mechanisms of the major antifungal drugs used in human therapy.

Antifungal agent	Mode of action and cellular target	Mechanism of resistance
polyenes	binding to ergosterol	absence of ergosterol (loss of function mutation in ERG3 or ERG6)
		decrease of ergosterol content in cells
azoles	inhibition of cytochrome p450 function: 14α-lanosterol demethylase (ERG11) sterol Δ^22 desaturase (ERG5)	efflux mediated by multidrug transporters
		decrease of affinity in Erg11p by mutations
		upregulation of ERG11
		alterations in the ergosterol biosynthetic pathway
allylamines	inhibition of squalene epoxidase (ERG1)	unknown
morpholines	inhibition of sterol Δ^14 reductase (ERG24) and the Δ^7-8 isomerase (ERG2)	unknown
5-fluorocytosine	inhibition of nucleic acids synthesis	defect in cytosine permease
		deficiency or lack of enzymes implicated in the metabolism of 5-FC
		deregulation of the pyrimidine biosynthetic pathway
echinocandins	inhibition of β-1,3 glucan synthase (FKS1&2)	alteration of affinity of echinocandins for β(1,3)-glucan synthase