Echinocandins (caspofungin, micafungin, anidulafungin) are fungicidal against Candida and fungistatic against Aspergillus. Their mechanism is:
- A Non-competitive inhibition of β-(1,3)-D-glucan synthase, disrupting fungal cell wall glucan polymer synthesis ✓
- B Inhibition of 14α-demethylase, preventing ergosterol synthesis
- C Binding to ergosterol in the fungal cell membrane, forming pores that cause potassium and proton loss
- D Inhibition of fungal RNA synthesis via interfering with dihydroorotate dehydrogenase
Correct answer: A. Non-competitive inhibition of β-(1,3)-D-glucan synthase, disrupting fungal cell wall glucan polymer synthesis
Explanation
Echinocandins inhibit β-(1,3)-D-glucan synthase (encoded by FKS1/FKS2 genes), the enzyme that polymerises UDP-glucose into the cell wall glucan polymer. Glucan is essential for fungal cell wall integrity but is absent in mammalian cells, explaining excellent tolerability. The primary mechanism of resistance is FKS1 hot-spot mutations reducing drug affinity. Azoles inhibit 14α-demethylase (ergosterol synthesis); amphotericin B binds ergosterol in the membrane; 5-flucytosine is converted to 5-FU inhibiting DNA/RNA synthesis.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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