What is a common mechanism of resistance to azoles in Candida species?

In Candida species, a common mechanism of resistance to azole antifungals involves mutations in the enzyme lanosterol 14α-demethylase, which is crucial for ergosterol synthesis, alongside the action of efflux pumps. Azoles target this enzyme to inhibit ergosterol production, thereby disrupting fungal cell membrane integrity. When mutations occur in lanosterol 14α-demethylase, the efficacy of azole drugs is reduced since the altered enzyme can continue to function or is less affected by the presence of the drug.

Additionally, efflux pumps play a significant role in resistance as they actively transport the azole drugs out of the fungal cell, decreasing the intracellular concentration of the drug and allowing the fungus to survive despite azole exposure. This combination of mutations and enhanced drug efflux represents a significant adaptive response in Candida species, making it a prominent mechanism of resistance observed in clinical settings.