TABLE 4.

Mechanism of action of currently used antifungal agents and modes of resistance.

Antifungal class	Mecanism of action	Modes of resistance
Polyenes	Disrupts fungal cell membrane function by binding to ergosterol, forming pores through which H+ and K+ ions can escape, leading to cell death.	Decreased access to target - sequestration of ergosterol
		Increased filamentation Howard et al. (2020)
Pyrimidine analogues	Inhibits fungal RNA and DNA syntesis	Decreased drug uptake due to cytosine permease
		Decreased cytosine deaminase activity Chandra et al. (2009)
Allylamines	Inhibits squalene epoxidase, which is required for ergosterol synthesis, and causes squalene, a substance toxic to fungal cells, to accumulate intracellularly, leading to cell death.	Mutations in the squalene epoxidase gene result in failure to block ergosterol biosynthesis Rudramurthy et al. (2018)
Azoles	Inhibition of the enzyme lanosterol 14α-demethylase, which is essential for the formation of ergosterol present in the fungal cell membrane.	Overexpression and mutations of targeted proteins (ERG11)
		Upregulation of efflux pumps in cell membranes
		Lanosterol 14α-demethylase mutations Rocio et al. (2020)
Echinocandins	Interrupts fungal cell wall synthesis by inhibiting the β-1,3 glucan enzyme complex	Mutations induced in targeted proteins (Fks1 and Fks2)
		Howard et al. (2020)