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    Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus


    Mulvihill, Eoin and Moloney, Nicola M. and Owens, Rebecca A. and Dolan, Stephen K. and Russell, Lauren and Doyle, Sean (2017) Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus. Frontiers in Microbiology, 8 (418). ISSN 1664-302X

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    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.

    Item Type: Article
    Additional Information: Copyright © 2017 Mulvihill, Moloney, Owens, Dolan, Russell and Doyle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Cite as: Mulvihill ED, Moloney NM, Owens RA, Dolan SK, Russell L and Doyle S (2017) Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus. Front. Microbiol. 8:418. doi: 10.3389/fmicb.2017.00418
    Keywords: siderophore; fungal proteomics; NRPS; membrane proteins; oxidative stress;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 10909
    Identification Number: https://doi.org/10.3389/fmicb.2017.00418
    Depositing User: Rebecca Owens
    Date Deposited: 01 Jul 2019 17:19
    Journal or Publication Title: Frontiers in Microbiology
    Publisher: Frontiers
    Refereed: Yes
    Funders: Science Foundation Ireland (SFI)
    URI:

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