Yeasts are pathogenic microorganisms that may give rise to life-threatening infections. The treatment of these pathological conditions becomes particularly challenging when yeasts acquire a resistance to clinically approved antifungal agents. The natural compound amphotericin B (AmB) kills drug-resistant yeasts but its high toxicity limits its clinical use.
A study by Martin Burke, University of Illinois at Urbana-Champaign, Urbana, USA, and colleagues, may pave the way to the development of less toxic AmB derivatives. The researchers revealed that AmB antifungal activity relies on its ability to form large extracellular aggregates that act as a sponge, extracting ergosterol from yeast cellular membranes. As ergosterol is a lipid that plays an essential role in yeast physiology, its extraction kills the yeasts.
By revealing novel insights into the mechanism of action of AmB, this study may facilitate the development of drugs that are able to kill drug-resistant yeast strains but do not have toxic effects associated with AmB.
- Amphotericin forms an extramembranous and fungicidal sterol sponge,
Thomas M Anderson, Mary C Clay, Alexander G Cioffi, Katrina A Diaz, Grant S Hisao, Marcus D Tuttle, Andrew J Nieuwkoop, Gemma Comellas, Nashrah Maryum, Shu Wang, Brice E Uno, Erin L Wildeman, Tamir Gonen, Chad M Rienstra, Martin D Burke,
Nat. Chem. Biol. 2014, 10, 400–406.