Mode of action of sterol biosynthesis inhibitors and resistance phenomena in fungi
Abstract
Sterol biosynthesis inhibitors (SBIs) are major medical and agricultural agents for the control of fungal diseases. According to their respective target sites, four classes can be recognized as inhibitors of: squalene epoxidation, C14-demethylation, Δ 14-reduction and Δ 8 ⃗ Δ 7 - isomerisation, C4- demethylation. The intensive use of SBIs promotes the selection of resistance to these antifungal agents. The two main mechanisms which contribute to the phenomenon are reduced affinity of target sites to their respective inhibitors and enhanced drug efflux. These mechanisms alone (monogenic resistance with the possibility of mono - or poly- allelism) or in combination (polygenic resistance) determine various resistance factors and spectra of cross resistance and affect more or less the practical efficacy of SBIs.