title: The antifungal mechanism of action of zinc pyrithione.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity.
  
  
  METHODS
  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.
  
  
  RESULTS
  It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron-sulphur clusters of proteins essential for fungal metabolism.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Procter & Gamble Co., 11511 Reed Hartman Hwy, Cincinnati, OH 45241, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Reeder
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: R S
authors.initials: RS
authors.lastname: Youngquist
authors.forename: J R
authors.initials: JR
authors.lastname: Schwartz
authors.forename: R C
authors.initials: RC
authors.lastname: Rust
authors.forename: C W
authors.initials: CW
authors.lastname: Saunders
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008290:Malassezia / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D009181:Mycoses / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012536:Scalp Dermatoses / Q000188:drug therapy
chemical_list: D000935:Antifungal Agents; D009942:Organometallic Compounds; D011725:Pyridines; D003300:Copper; C010423:pyrithione zinc