The antifungal mechanism of action of zinc pyrithione.

Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT. The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity. Modern systems biology approaches, such as deletion library screening and microarray analysis, were used in combination with traditional measures of metal content, microbial growth and enzyme assays. It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron-sulphur clusters of proteins essential for fungal metabolism. The molecular basis for the antifungal activity of the commonly used active ZPT has been elucidated, more than 50 years since its introduction, as utilizing a copper toxicity mechanism that targets critical iron-sulphur proteins.