Table 7.

Main resistance mechanisms and genes involved in Aspergillus spp. (adapted from [141,142,143]).

Antifungal Class	Molecular Resistance Mechanism	Phenotype
Azoles	cyp51A point mutations	Decreased target enzyme 14α-demethylase affinity for drug
	cyp51A tandem repeat in the promoter region with or without accompanying mutations	Increases the protein level of expression and alters the docking of azoles conferring resistance
	Non-cyp51A: Overexpression of ATP binding cassette	Decrease in intracellular drug concentrations (efflux pump upregulation)
Echinocandins	FKS1 mutation dependent-mutations in hotspot regions	BDG synthase enzyme with highly reduced sensitivity to echinocandin drugs
	FKS1 mutation independent-caspofungin mediated alteration of the glucan synthetase lipid microenvironment and off-target effect on mitochondria leading to increased reactive oxygen species	Alters the enzyme drug-binding affinity