What is the primary mechanism by which azoles inhibit fungal growth?

• A. Inhibit beta-glucan synthase
• B. Inhibit lanosterol 14-alpha-demethylase (ERG11), reducing ergosterol synthesis
• C. Block DNA replication by inhibiting thymidylate synthase
• D. Disrupt microtubule polymerization during mitosis

Answer: (B)

Azoles inhibit fungal growth by blocking ergosterol synthesis. They target lanosterol 14-alpha-demethylase (ERG11), a fungal cytochrome P450 enzyme that converts lanosterol into ergosterol, a critical component of the fungal cell membrane. When this enzyme is inhibited, ergosterol levels drop and toxic sterol intermediates build up, disrupting membrane structure and function. This membrane disruption hinders essential processes and slows or stops growth. The fungal enzyme has enough difference from human enzymes to allow selective inhibition, which is why azoles are effective antifungals with manageable toxicity. Other mechanisms described belong to different drug classes (for example, drugs that block beta-glucan synthesis or that affect DNA or microtubules), not to azoles.