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 Δ22 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 Δ14 reductase (ERG24) and the Δ7–8 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 |