Abstract
The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system. FC levels were unaffected following deletion of all other genes encoding microsome-associated proteins. MirC does not appear to play a role in either siderophore export from, or uptake into, A. fumigatus. Label-free quantitative proteomic analysis unexpectedly revealed increased abundance of siderophore biosynthetic enzymes. In addition, increased expression of hapX (7.2 and 13.8-fold at 48 and 72 h, respectively; p < 0.001) was observed in ΔmirC compared to wild-type under iron-replete conditions by qRT-PCR. This was complemented by significantly elevated extracellular triacetylfusarinine C (TAFC; p < 0.01) and fusarinine C (FSC; p < 0.05) siderophore secretion. We conclude that MirC plays an important role in FC biosynthesis and contributes to the maintenance of iron homeostasis in A. fumigatus.
Highlights
Many iron-requiring fungi utilize high affinity iron acquisition strategies to procure essential iron
Either A. fumigatus strain was co-transformed with two DNA constructs, each containing an incomplete fragment of a pyrithiamine resistance gene (Kubodera et al, 2002) fused to 1 kb of up and downstream sequences which flanked the regions to be deleted
Selection of Genes to Further Study the Ability of A. fumigatus to Survive in Iron-Deplete Conditions
Summary
Many iron-requiring fungi utilize high affinity iron acquisition strategies to procure essential iron. An ability to exist in two oxidative states; ferric (Fe3+) and ferrous (Fe2+), means that iron can drive the generation of deleterious reactive oxygen species (Halliwell and Gutteridge, 1984). Iron is required as a co-factor for antioxidant enzymes, such as peroxidases and catalases, in the form of heme. Careful management of the utilization of high affinity iron uptake mechanisms is an important facet of iron metabolism. SreA and HapX are core players underlying the global “omic” shift observed when Aspergillus species face iron starvation (Oberegger et al, 2001; Schrettl et al, 2008, 2010). SreA is a GATA-type transcription factor that represses high affinity iron
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
