Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins

• DOI: 10.1128/aac.00724-11
• Publication Date: 2011-09-27T03:50:46Z
• Authors: Nancy L. Reeder; Jerry Kaplan; Jun Xu; R. Scott Youngquist; Jared Wallace; Ping Hu; Kenton D. Juhlin; James R. Schwartz; Raymond A. Grant; Angela Fieno; Suzanne Nemeth; Tim Reichling; Jay P. Tiesman; Tim Mills; Mark Steinke; Shuo L. Wang; Charles W. Saunders
• Keywords: Iron-Sulfur Proteins; 0301 basic medicine; Antifungal Agents; Malassezia; Pyridines; Saccharomyces cerevisiae; Fungal Proteins; 03 medical and health sciences; Gene Expression Regulation, Fungal; Organometallic Compounds; Humans; Copper; Oligonucleotide Array Sequence Analysis; Sequence Deletion

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