DNA microarray analysis suggests that zinc pyrithione causes iron starvation to the yeast Saccharomyces cerevisiae

J Biosci Bioeng. 2010 May;109(5):479-86. doi: 10.1016/j.jbiosc.2009.10.025. Epub 2009 Nov 22.

Abstract

Zinc pyrithione has been used in anti-dandruff shampoos and in anti-fouling paint on ships. However, little is known of its mode of action. We characterized the effects of sub-lethal concentrations of zinc pyrithione (Zpt) on Saccharomyces cerevisiae using DNA microarrays. The majority of the strongly upregulated genes are related to iron transport, and many of the strongly downregulated genes are related to the biosynthesis of cytochrome (heme). These data suggest that Zpt induces severe iron starvation. To confirm the DNA microarray data, we supplemented cultures containing Zpt with iron, and the growth of the yeast was restored significantly. From these results, we propose that the principal toxicity of zinc pyrithione arises from iron starvation.

MeSH terms

  • Antifungal Agents / administration & dosage
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Fungal / drug effects
  • Gene Expression Regulation, Fungal / physiology
  • Iron / metabolism*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Organometallic Compounds / administration & dosage*
  • Pyridines / administration & dosage*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Antifungal Agents
  • Organometallic Compounds
  • Pyridines
  • Saccharomyces cerevisiae Proteins
  • Iron
  • pyrithione zinc