SreA‐mediated iron regulation in Aspergillus fumigatus

Abstract

Summary Aspergillus fumigatus , the most common airborne fungal pathogen of humans, employs two high‐affinity iron uptake systems: iron uptake mediated by the extracellular siderophore triacetylfusarinine C and reductive iron assimilation. Furthermore, A. fumigatus utilizes two intracellular siderophores, ferricrocin and hydroxyferricrocin, to store iron. Siderophore biosynthesis, which is essential for virulence, is repressed by iron. Here we show that this control is mediated by the GATA factor SreA. During iron‐replete conditions, SreA deficiency partially derepressed synthesis of triacetylfusarinine C and uptake of iron resulting in increased cellular accumulation of both iron and ferricrocin. Genome‐wide DNA microarray analysis identified 49 genes that are repressed by iron in an SreA‐dependent manner. This gene set, termed SreA regulon, includes all known genes involved in iron acquisition, putative novel siderophore biosynthetic genes, and also genes not directly linked to iron metabolism. SreA deficiency also caused upregulation of iron‐dependent and antioxidative pathways, probably due to the increased iron content and iron‐mediated oxidative stress. Consistently, the sreA disruption mutant displayed increased sensitivity to iron, menadion and phleomycin but retained wild‐type virulence in a mouse model. As all detrimental effects of sreA disruption are restricted to iron‐replete conditions these data underscore that A. fumigatus faces iron‐depleted conditions during infection.

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Cited by papers we hold 11

• Uptake of the Siderophore Triacetylfusarinine C, but Not Fusarinine C, Is Crucial for Virulence of Aspergillus fumigatus · 2022
  Not checked
• A fungal ABC transporter FgAtm1 regulates iron homeostasis via the transcription factor cascade FgAreA-HapX. · 2019
  Not checked
• Metals in fungal virulence · 2017
  No notice
• Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines · 2015
  No notice
• ChIP-seq and In Vivo Transcriptome Analyses of the Aspergillus fumigatus SREBP SrbA Reveals a New Regulator of the Fungal Hypoxia Response and Virulence · 2014
  Corrected
• Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance · 2013
  No notice
• Transcriptional and proteomic analysis of the Aspergillus fumigatus ΔprtT protease-deficient mutant. · 2012
  Not checked
• SREBP Coordinates Iron and Ergosterol Homeostasis to Mediate Triazole Drug and Hypoxia Responses in the Human Fungal Pathogen Aspergillus fumigatus · 2011
  No notice
• The MAP kinase MpkA controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in Aspergillus fumigatus · 2011
  No notice
• HapX Positively and Negatively Regulates the Transcriptional Response to Iron Deprivation in Cryptococcus neoformans · 2010
  No notice
• HapX-Mediated Adaption to Iron Starvation Is Crucial for Virulence of Aspergillus fumigatus · 2010
  No notice

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