Natamycin Blocks Fungal Growth by Binding Specifically to

Natamycin is a polyene antibiotic that is commonly used as an antifungal agent because of its broad spectrum of activity and the lack of development of resistance.Other polyene antibiotics, like nystatin and filipin are known to interact with sterols, with some specificity for ergosterol thereby causing leakage of essen-tial components and cell death. The mode of action of natamy-cin is unknownand is investigated in this studyusingdifferent in vitro and in vivo approaches. Isothermal titration calorimetry and direct binding studies revealed that natamycin binds specif-ically to ergosterol present in model membranes. Yeast sterol biosynthetic mutants revealed the importance of the double bonds in the B-ring of ergosterol for the natamycin-ergosterol interaction and the consecutive block of fungal growth. Surpris-ingly, in strong contrast to nystatin and filipin, natamycin did not change the permeability of the yeast plasma membran