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Mechanisms of Action: Physiological Effects

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

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
Nancy L. Reeder
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Jerry Kaplan
2Department of Pathology, 50 N. Medical Drive, School of Medicine, University of Utah, Salt Lake City, Utah
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Jun Xu
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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R. Scott Youngquist
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Jared Wallace
2Department of Pathology, 50 N. Medical Drive, School of Medicine, University of Utah, Salt Lake City, Utah
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Ping Hu
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Kenton D. Juhlin
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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James R. Schwartz
3Procter & Gamble Co., Sharon Woods Innovation Center, Cincinnati, Ohio
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Raymond A. Grant
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Angela Fieno
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Suzanne Nemeth
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Tim Reichling
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Jay P. Tiesman
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Tim Mills
4Procter & Gamble Co., Fabric & Home Care Innovation Center, Cincinnati, Ohio
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Mark Steinke
3Procter & Gamble Co., Sharon Woods Innovation Center, Cincinnati, Ohio
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Shuo L. Wang
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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Charles W. Saunders
1Procter & Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio
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  • For correspondence: saunders.cw@pg.com
DOI: 10.1128/AAC.00724-11
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ABSTRACT

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.

FOOTNOTES

    • Received 25 May 2011.
    • Returned for modification 23 July 2011.
    • Accepted 14 September 2011.
    • Accepted manuscript posted online 26 September 2011.
  • ↵† Supplemental material for this article may be found at http://dx.doi.org/10.1128/AAC.00724-11.

  • Copyright © 2011, American Society for Microbiology. All Rights Reserved.
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Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins
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
Antimicrobial Agents and Chemotherapy Nov 2011, 55 (12) 5753-5760; DOI: 10.1128/AAC.00724-11

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Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins
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
Antimicrobial Agents and Chemotherapy Nov 2011, 55 (12) 5753-5760; DOI: 10.1128/AAC.00724-11
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