Screening method to identify inhibitors of siderophore biosynthesis in the opportunistic fungal pathogen,Aspergillus fumigatus

2009 ◽  
Vol 49 (1) ◽  
pp. 8-13 ◽  
Author(s):  
L.J. Pinto ◽  
M.M. Moore
Keyword(s):  
Aspergillus Fumigatus ◽  
Fungal Pathogen ◽  
Screening Method ◽  
Siderophore Biosynthesis ◽  
Opportunistic Fungal Pathogen

scholarly journals Aspergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicity

mBio ◽  
2021 ◽  
Author(s):  
Laure Nicolas Annick Ries ◽  
Patricia Alves de Castro ◽  
Lilian Pereira Silva ◽  
Clara Valero ◽  
Thaila Fernanda dos Reis ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Fungal Pathogen ◽  
Carbon Sources ◽  
Body Fluids ◽  
Peripheral Tissues ◽  
Content Type ◽  
Virulence Traits ◽  
Acetate Utilization ◽  
Opportunistic Fungal Pathogen

Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion.

A copper transcription factor, AfMac1, regulates both iron and copper homeostasis in the opportunistic fungal pathogen Aspergillus fumigatus

2018 ◽  
Vol 475 (17) ◽  
pp. 2831-2845 ◽  
Author(s):  
Yong-Sung Park ◽  
Suzie Kang ◽  
Hyewon Seo ◽  
Cheol-Won Yun
Keyword(s):  
Gene Expression ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogen ◽  
Promoter Region ◽  
Regulation Of Gene Expression ◽  
Copper Homeostasis ◽  
Living Cells ◽  
The Other ◽  
Binding Motif ◽  
Opportunistic Fungal Pathogen

Although iron and copper are co-ordinately regulated in living cells, the homeostatic effects of each of these metals on the other remain unknown. Here, we show the function of AfMac1, a transcriptional activator of the copper and iron regulons of Aspergillus fumigatus, on the interaction between iron and copper. In addition to the copper-specific AfMac1-binding motif 5′-TGTGCTCA-3′ found in the promoter region of ctrC, the iron-specific AfMac1-binding motif 5′-AT(C/G)NN(A/T)T(A/C)-3′ was identified in the iron regulon but not in the copper regulon by ChIP sequence analysis. Furthermore, mutation of the AfMac1-binding motif of sit1 eliminated AfMac1-mediated sit1 up-regulation. Interestingly, the regulation of gene expression in the iron regulon by AfMac1 was not affected by copper and vice versa. AfMac1 localized to the nucleus under iron- or copper-depleted conditions, and AfMac1 was mostly detected in the cytoplasm under iron- or copper-replete conditions. Taken together, these results suggest that A. fumigatus independently regulates iron and copper homeostasis in a manner that involves AfMac1 and mutual interactions.

scholarly journals SidL, an Aspergillus fumigatus Transacetylase Involved in Biosynthesis of the Siderophores Ferricrocin and Hydroxyferricrocin

2011 ◽  
Vol 77 (14) ◽  
pp. 4959-4966 ◽  
Author(s):  
Michael Blatzer ◽  
Markus Schrettl ◽  
Bettina Sarg ◽  
Herbert H. Lindner ◽  
Kristian Pfaller ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Fluorescent Protein ◽  
Iron Starvation ◽  
Fungal Virulence ◽  
Content Type ◽  
Siderophore Biosynthesis ◽  
Opportunistic Fungal Pathogen ◽  
Triacetylfusarinine C ◽  
Green Fluorescent ◽  
Biosynthetic Machinery

ABSTRACTThe opportunistic fungal pathogenAspergillus fumigatusproduces four types of siderophores, low-molecular-mass iron chelators: it excretes fusarinine C (FsC) and triacetylfusarinine C (TAFC) for iron uptake and accumulates ferricrocin (FC) for hyphal and hydroxyferricrocin (HFC) for conidial iron distribution and storage. Siderophore biosynthesis has recently been shown to be crucial for fungal virulence. Here we identified a new component of the fungal siderophore biosynthetic machinery: AFUA_1G04450, termed SidL. SidL is conserved only in siderophore-producing ascomycetes and shows similarity to transacylases involved in bacterial siderophore biosynthesis and theN5-hydroxyornithine:anhydromevalonyl coenzyme A-N5-transacylase SidF, which is essential for TAFC biosynthesis. Inactivation of SidL inA. fumigatusdecreased FC biosynthesis during iron starvation and completely blocked FC biosynthesis during iron-replete growth. In agreement with these findings, SidL deficiency blocked conidial accumulation of FC-derived HFC under iron-replete conditions, which delayed germination and decreased the size of conidia and their resistance to oxidative stress. Remarkably, thesidLgene is not clustered with other siderophore-biosynthetic genes, and its expression is not affected by iron availability. Tagging of SidL with enhanced green fluorescent protein suggested a cytosolic localization of the FC-biosynthetic machinery. Taken together, these data suggest that SidL is a constitutively activeN5-hydroxyornithine-acetylase required for FC biosynthesis, in particular under iron-replete conditions. Moreover, this study revealed the unexpected complexity of siderophore biosynthesis, indicating the existence of an additional, iron-repressedN5-hydroxyornithine-acetylase.

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