Zinc pyrithione inhibits yeast growth through copper influx and inactivation of iron-sulfur proteins

Antimicrob Agents Chemother. 2011 Dec;55(12):5753-60. doi: 10.1128/AAC.00724-11. Epub 2011 Sep 26.


Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antifungal Agents / pharmacology*
  • Copper / metabolism*
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Humans
  • Iron-Sulfur Proteins / antagonists & inhibitors*
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism
  • Malassezia / drug effects*
  • Malassezia / genetics
  • Malassezia / growth & development
  • Oligonucleotide Array Sequence Analysis
  • Organometallic Compounds / pharmacology*
  • Pyridines / pharmacology*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Sequence Deletion


  • Antifungal Agents
  • Fungal Proteins
  • Iron-Sulfur Proteins
  • Organometallic Compounds
  • Pyridines
  • Copper
  • pyrithione zinc