Sheridan, Kevin J. and Lechner, Beatrix Elizabeth and O'Keeffe, Grainne and Keller, Markus A. and Werner, Ernst R. and Lindner, Herbert and Jones, Gary W. and Haas, Hubertus and Doyle, Sean (2016) Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus. Scientific Reports, 6 (35306). ISSN 2045-2322

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Abstract

Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation. Quantitative proteomic analysis revealed substantial proteomic remodelling in ΔegtA compared to wild-type under both basal and ROS conditions, whereby the abundance of 290 proteins was altered. Specifically, the reciprocal differential abundance of cystathionine γ-synthase and β-lyase, respectively, influenced cystathionine availability to effect EGT biosynthesis. A combined deficiency in EGT biosynthesis and the oxidative stress response regulator Yap1, which led to extreme oxidative stress susceptibility, decreased resistance to heavy metals and production of the extracellular siderophore triacetylfusarinine C and increased accumulation of the intracellular siderophore ferricrocin. EGT dissipated H2O2 in vitro, and elevated intracellular GSH levels accompanied abrogation of EGT biosynthesis. EGT deficiency only decreased resistance to high H2O2 levels which suggests functionality as an auxiliary antioxidant, required for growth at elevated oxidative stress conditions. Combined, these data reveal new interactions between cellular redox homeostasis, secondary metabolism and metal ion homeostasis.

Item Type:	Article
Additional Information:	How to cite this article: Sheridan, K. J. et al. Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus. Sci. Rep. 6, 35306; doi: 10.1038/srep35306 (2016). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ © The Author(s) 2016
Keywords:	Ergothioneine Biosynthesis; Aspergillus fumigatus;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	11163
Identification Number:	https://doi.org/10.1038/srep35306
Depositing User:	Dr. Sean Doyle
Date Deposited:	08 Oct 2019 15:23
Journal or Publication Title:	Scientific Reports
Publisher:	Nature Publishing Group
Refereed:	Yes
Funders:	Science Foundation Ireland (SFI), Austrian Science Foundation
URI:	https://www.nature.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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