Understanding the Mechanism of Action of the Anti-Dandruff Agent Zinc Pyrithione against Malassezia restricta

Minji Park,Yong-Joon Cho,Yang Won Lee,Won Hee Jung

doi:10.1038/s41598-018-30588-2

Minji Park, Yong-Joon Cho + Show 2 more

Open Access

https://doi.org/10.1038/s41598-018-30588-2

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Abstract

Dandruff is known to be associated with Malassezia restricta. Zinc pyrithione (ZPT) has been used as an ingredient in anti-dandruff treatments. The mechanism of ZPT has been investigated in several studies; however, a non-pathogenic model yeast, such as Saccharomyces cerevisiae was most often used. The aim of the present study was to understand how ZPT inhibits the growth of M. restricta. We analyzed the cellular metal content and transcriptome profile of ZPT-treated M. restricta cells and found that ZPT treatment dramatically increased cellular zinc levels, along with a small increase in cellular copper levels. Moreover, our transcriptome analysis showed that ZPT inhibits Fe-S cluster synthesis in M. restricta. We also observed that ZPT treatment significantly reduced the expression of lipases, whose activities contribute to the survival and virulence of M. restricta on human skin. Therefore, the results of our study suggest that at least three inhibitory mechanisms are associated with the action of ZPT against M. restricta: (i) an increase in cellular zinc levels, (ii) inhibition of mitochondrial function, and (iii) a decrease in lipase expression.

Highlights

Zinc pyrithione is a derivative of pyrithione (1-hydroxy-2-pyridinethione), which is synthesized from the antimicrobial metabolite ‘aspergillic acid’ of Aspergillus flavus[14,15,16,17]
Zinc pyrithione (ZPT) treatment led to an increase in cellular zinc levels in M. restricta
The metal content of ZPT-treated S. cerevisiae cells was measured in parallel with inductively coupled plasma-atomic emission spectroscopy (ICP-AES) to replicate data previously reported by Reeder et al.[25]

Summary

Introduction

Zinc pyrithione is a derivative of pyrithione (1-hydroxy-2-pyridinethione), which is synthesized from the antimicrobial metabolite ‘aspergillic acid’ of Aspergillus flavus[14,15,16,17]. Another study by Reeder et al.[25] showed that iron levels in ZPT-treated S. cerevisiae cells were not changed, they observed an upregulation of expression of Fet[3], a ferroxidase in the high-affinity reductive iron transport system, which suggested that iron starvation might not be a direct cause of ZPT toxicity. A number of deletion mutants that lack genes involved in iron-sulfur cluster (Fe-S) assembly in mitochondria showed significant growth defects following ZPT treatment These results suggested that, in addition to copper toxicity, copper-mediated inactivation of Fe-S cluster assembly in mitochondria contributes to growth inhibition by ZPT, at least in S. cerevisiae. This is the first comprehensive study to directly investigate the mechanism of action of ZPT against M. restricta

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