BACKGROUND: Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT. OBJECTIVES: The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity. METHODS: Modern systems biology approaches, such as deletion library screening and microarray analysis, were used in combination with traditional measures of metal content, microbial growth and enzyme assays. RESULTS: It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron-sulphur clusters of proteins essential for fungal metabolism. CONCLUSIONS: The molecular basis for the antifungal activity of the commonly used active ZPT has been elucidated, more than 50 years since its introduction, as utilizing a copper toxicity mechanism that targets critical iron-sulphur proteins.
BACKGROUND:Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT. OBJECTIVES: The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity. METHODS: Modern systems biology approaches, such as deletion library screening and microarray analysis, were used in combination with traditional measures of metal content, microbial growth and enzyme assays. RESULTS: It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron-sulphur clusters of proteins essential for fungal metabolism. CONCLUSIONS: The molecular basis for the antifungal activity of the commonly used active ZPT has been elucidated, more than 50 years since its introduction, as utilizing a coppertoxicity mechanism that targets critical iron-sulphur proteins.
Authors: Abigail C Jackson; Jacqueline M Zaengle-Barone; Elena A Puccio; Katherine J Franz Journal: ACS Infect Dis Date: 2020-04-29 Impact factor: 5.084
Authors: Jacqueline M Zaengle-Barone; Abigail C Jackson; David M Besse; Bradford Becken; Mehreen Arshad; Patrick C Seed; Katherine J Franz Journal: ACS Infect Dis Date: 2018-03-26 Impact factor: 5.084
Authors: Wei Sun; Rebecca A Weingarten; Miao Xu; Noel Southall; Sheng Dai; Paul Shinn; Philip E Sanderson; Peter R Williamson; Karen M Frank; Wei Zheng Journal: Emerg Microbes Infect Date: 2016-11-09 Impact factor: 7.163
Authors: Natalie G Robinett; Edward M Culbertson; Ryan L Peterson; Hiram Sanchez; David R Andes; Jeniel E Nett; Valeria C Culotta Journal: J Biol Chem Date: 2018-12-28 Impact factor: 5.157