Linkage between genes involved in azole resistance and ergosterol biosynthesis
W. Scott Moye‐Rowley
Abstract
Azole drugs act by blocking the biosynthesis of ergosterol, the sterol component of the fungal plasma membrane. Resistance to azole drugs appears frequently in fungi and can be typically acquired by changes in the coding sequence of the gene producing lanosterol 14-demethylase, the azole target enzyme, or changes in the expression of this gene that is designated ERG11 A second route of resistance involves increased expression of loci encoding ATPbinding cassette (ABC) transporters, which are thought to efflux drugs and prevent toxic intracellular concentrations from being achieved These 2 resistance mechanisms have generally been considered to represent independent, unlinked modes of lowering azole susceptibility. Recent work in several different fungi support a different viewpoint: that these resistance modalities actually illuminate a physiological tie between the biosynthesis of ergosterol and expression of ABC transporter proteins.