The inhibitory effect of cerulenin to yeasts is fungicidal

Abstract

Fatty acid biosynthesis plays a significant role in the growth and survival of diverse organisms. In yeasts, the de novo fatty acid synthesis (FAS) pathway produces and regulates essential fatty acid species such as saturated (SFA) and unsaturated (UFA) fatty acids that are required for generation and maintenance of cell membranes. Inhibition of enzymes in this pathway, such as fatty acid synthase and fatty acid desaturase, impede yeast cell growth unless appropriate exogenous fatty acids are provided.^1,2 Although, the fatty acid biosynthesis pathway is essential to yeast cells, exploration of this pathway for combating fungal infections has been largely neglected. We and others have shown that deletion of a fatty acid synthase dramatically attenuates the virulence of the yeast Candida parapsilosis 2 and Candida albicans.¹ Significantly, our data has revealed that inhibition of FAS enzymes results in the hypersensitivity of the yeast to serum, indicating that targeting this pathway is potentially an ideal way to combat systemic yeast infections.² We demonstrated that using the minimal inhibitory concentration of cerulenin, a fatty acid synthase inhibitor, we could kill the wild type yeast cells in serum.² Thus, the inhibitory effect of cerulenin (ie. blockade of the FAS pathway) on the yeast cells is fungicidal.