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

Yasokawa, Daisuke; Murata, Satomi; Iwahashi, Yumiko; Kitagawa, Emiko; Kishi, Kiyozo; Okumura, Yasuko; Iwahashi, Hitoshi

doi:10.1016/j.jbiosc.2009.10.025

Cited by 34 publications

(31 citation statements)

References 53 publications

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“…In this communication, we confirm the observation by Yasokawa et al (43) that ZPT increases transcription of the iron regulon: however, we ascribe that increase not to a transcriptional response to low iron concentrations but rather to a decrease in the activity of iron-sulfur (Fe-S) cluster-containing proteins. We show that ZPT-mediated growth inhibition is due to increased copper uptake and that copper inactivates key Fe-S proteins by a mechanism similar to that described for copper-mediated growth inhibition in bacteria (7,26).…”

supporting

confidence: 91%

“…High intracellular zinc levels can inhibit microbial growth, likely due to zinc binding to intracellular proteins and resulting in mismetallation (31). Yasokawa et al (43) recently used transcriptional analysis of ZPT-treated Saccharomyces cerevisiae to suggest that ZPT causes iron starvation. They further showed that an iron salt lowered the antiyeast activity of ZPT, suggesting that iron starvation is a key component of ZPT's mechanism of action.…”

mentioning

confidence: 99%

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

Reeder

Kaplan

et al. 2011

Antimicrob Agents Chemother

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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 metalligand complex that inhibits fungal growth by increasing the cellular level of a different metal.Fungi have an essential role in causing dandruff, a scalp disease affecting Ͼ40% of the world's adult population (36). Zinc pyrithione (ZPT) is an antimicrobial compound that has been used since the 1960s in antidandruff shampoos (36) and in antifouling paints (37). In dandruff subjects, ZPT treatment reduces the amount of fungus on the scalp and stops dandruff flaking (6). Despite billions of human scalp treatments for over 4 decades, little is known of the mechanism by which ZPT inhibits fungal growth.Malassezia globosa and M. restricta are the two most common fungi on scalp (15). Despite a recent description of the genome sequences of these two species (42), study of Malassezia is challenging due to the absence of transformation methods and available mutants. Several attempts have been made to characterize the mode of action of ZPT against model fungi. ZPT has been reported to inhibit transport by membrane depolarization (5, 11). However, efficacy was reported only with doses of at least 100 M, whereas microbial growth inhibition is observed at much lower ZPT doses. Pyrithione is a well-known zinc ionophore that causes increased zinc levels within mammalian cells (1,18,27). High intracellular zinc levels can inhibit microbial growth, likely due to zinc binding to intracellular proteins and resulting in mismetallation (31). Yasokawa et al. (43) recently used transcriptional analysis of ZPT-treated Saccharomyces cerevisiae to suggest that ZPT causes iron starvation. They further showed that an iron salt lowered the antiyeast activity of ZPT, suggesting that iron starvation is a key component of ZPT's mechanism of action.In this communication, we confirm the observation by Yasokawa et al. (43) that ZPT increases transcription of the iron regulon: however, we ascribe that increase not to a transcriptional response to low iron concentrations but rather to a decrease in the activity of iron-sulfur (Fe-S) cluster-containing proteins. We show that ZPT-mediated growth inhibition is due to increased copper uptake and that copper inactivates key F...

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supporting

confidence: 91%

mentioning

confidence: 99%

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

Reeder

Kaplan

et al. 2011

Antimicrob Agents Chemother

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“…It was shown that zinc pyrithione leads to decrease in intracellular adenosine triphosphate amount in Gram-negative bacteria species Escherichia coli and Pseudomonas aeruginosa 7 . Also, the treatment with ZnPT induces the production of reactive oxygen species (ROS) 34,35 , which are related to the antibacterial action 36 . Thus, the ROS from zinc ions, such as hydrogen peroxide, would be associated to the toxic effects of ZnPT 37 .…”

Section: Resultsmentioning

confidence: 99%

“…In that case, the metal starvation 34 or high intracellular availability 8,45 will affect the activity of iron-sulfur proteins involved in diverse metabolic functions required for microbial growth 46 . Ion exchange is a slow process and this can enlarge the biocidal effect of metal-based antimicrobials 47 .…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial Performance of Thermoplastic Elastomers Containing Zinc Pyrithione and Silver Nanoparticles

et al. 2017

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The purpose of the present study was to evaluate the antimicrobial potential of styrene-ethylene/ butylene-styrene based thermoplastic elastomers (TPE) incorporated with zinc pyrithione (ZnPT) and silver nanoparticles (AgNano). Japan Industrial Standard was applied to evaluate the antimicrobial potential of incorporated TPE compounds against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Antifungal action was evaluated against Aspergillus niger, Candida albicans and Cladosporium cladosporioides. Samples prepared with ZnPT eliminated 99.9% of the E. coli and 99.7 % of the S. aureus population, and presented an inhibition zone in the fungal assay. Samples prepared with AgNano eliminated 99.7% of the E. coli and 95.5 % of the S. aureus population. There was no inhibition zone in samples containing AgNano; however, these samples did not present fungal growth on their surfaces. TPE samples containing ZnPT showed biocidal activity against the microorganisms tested and can be used to develop antimicrobial products.

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“…The biocide ZnPT was found to inhibit ATP synthesis in the mitochondrion by opening up small pores in the membrane [39]. In the yeast Sacharomyces cerevisiae the biocide was found to up-regulate genes related to ion transport and down-regulate genes related to the biosynthesis of cytochrome [40]. ZnPT has been shown to cause accumulation of zinc in the tissues of Mytilus galloprovincialis, being transported from the gills via the hemolymph to the digestive gland, which functions as the main center for metabolic regulation [37].…”

Section: Znpt and Cupt Loaded Nanomaterialsmentioning

confidence: 99%

Antimacrofouling Efficacy of Innovative Inorganic Nanomaterials Loaded with Booster Biocides

Gutner-Hoch

Freitas

Oliveira

et al. 2018

JMSE

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Abstract:The application of nano-structured compounds has been increasing rapidly in recent years, in several fields. The use of engineered nano-materials as carriers of antifouling compounds is just beginning and already reveals clear advantages compared to bulk active compounds, such as slowed and controlled release, novel functionality, and high loading capacity. This present study assesses the antifouling efficacy of two nanostructured materials, spherical mesoporous silica nanocapsules (SiNC) and Zn-Al layered double hydroxides (LDH), loaded with two commercial biocides, zinc prithione (ZnPT) and copper pyrithione (CuPT). The study used adult mussels from three geographical regions, the Atlantic Ocean, Mediterranean Sea, and the Red Sea, to examine the efficacy of the innovative compounds. The efficacy of these compounds on larvae of the bryozoan Bugula neritina from the Mediterranean Sea and the Red Sea was also examined. The results of this study demonstrated the environmentally friendly properties of unloaded LDH against the two-model systems, adult mussels or bryozoan larvae. ZnPT entrapped in LDH demonstrated the most effective antifouling compound against the two model systems. A comparison of the impact of the two compounds on macrofouling organisms from the different marine habitats examined in this study indicates a distinction associated with the organisms' different ecosystems. The Red Sea mussels and bryozoans, representing a tropical marine ecosystem, yielded the highest efficacy values among tested Atlantic Ocean and Mediterranean Sea mussels and bryozoans.

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

Cited by 34 publications

References 53 publications

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

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

Antimicrobial Performance of Thermoplastic Elastomers Containing Zinc Pyrithione and Silver Nanoparticles

Antimacrofouling Efficacy of Innovative Inorganic Nanomaterials Loaded with Booster Biocides

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