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    Gliotoxin effects on fungal growth: Mechanisms and exploitation


    Carberry, Stephen and Molloy, Emer and Hammel, Stephen and O'Keefe, Grainne and Jones, Gary W. and Kavanagh, Kevin and Doyle, Sean (2012) Gliotoxin effects on fungal growth: Mechanisms and exploitation. Fungal Genetics and Biology, 49 (4). pp. 302-312. ISSN 1087-1845

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    Abstract

    Although initially investigated for its antifungal properties, little is actually known about the effect of gliotoxin on Aspergillus fumigatus and other fungi. We have observed that exposure of A. fumigatus to exogenous gliotoxin (14 lg/ml), under gliotoxin-limited growth conditions, results in significant alteration of the expression of 27 proteins (up- and down-regulated >1.9-fold; p < 0.05) including de novo expression of Cu, Zn superoxide dismutase, up-regulated allergen Asp f3 expression and down-regulated catalase and a peroxiredoxin levels. Significantly elevated glutathione GSH levels (p < 0.05), along with concomitant resistance to diamide, were evident in A. fumigatus ∆gliT, lacking gliotoxin oxidoreductase, a gliotoxin self-protection gene. Saccharomyces cerevisiae deletents (∆sod1 and ∆yap1) were hypersensitive to exogenous gliotoxin, while ∆gsh1 was resistant. Significant gliotoxin-mediated (5 µg/ml) growth inhibition (p < 0.001) of Aspergillus nidulans, Aspergillus terreus, Aspergillus niger, Cochliobolus heterostrophus and Neurospora crassa was also observed. Growth of Aspergillus flavus, Fusarium graminearum and Aspergillus oryzae was significantly inhibited (p < 0.001) at gliotoxin (10 lg/ml), indicating differential gliotoxin sensitivity amongst fungi. Re-introduction of gliT into A. fumigatus DgliT, at a different locus (ctsD; AFUA_4G07040, an aspartic protease), with selection on gliotoxin, facilitated deletion of ctsD without use of additional antibiotic selection markers. Absence of ctsD expression was accompanied by restoration of gliT expression, and resistance to gliotoxin. Thus, we propose gliT/gliotoxin as a useful selection marker system for fungal transformation. Finally, we suggest incorporation of gliotoxin sensitivity assays into all future fungal functional genomic studies.

    Item Type: Article
    Additional Information: The definitive version of this article is available at doi:10.1016/j.fgb.2012.02.003
    Keywords: Aspergillus fumigatus; Proteomics; Natural products; Aspergillus; Yeast; NRPS;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 4233
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 05 Mar 2013 16:26
    Journal or Publication Title: Fungal Genetics and Biology
    Publisher: Elsevier Inc.
    Refereed: Yes
    URI:

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