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    The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence


    Alves de Castro, Patricia and dos Reis, Thaila Fernanda and Dolan, Stephen K. and Manfiolli, Adriana Oliveira and Brown, Neil Andrew and Jones, Gary W. and Doyle, Sean and Riaño‐Pachón, Diego M. and Squina, Fabio M. and Caldana, Camila and Singh, Ashutosh and Del Poeta, Maurizio and Hagiwara, Daisuke and Silva-Rocha, Rafael and Goldman, Gustavo H. (2016) The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence. Molecular Microbiology, 102 (4). pp. 642-671. ISSN 1365-2958

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    Abstract

    The serine‐threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP‐dependent PKA, cGMP‐ dependent protein kinase G and phospholipid‐dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism. The ΔschA null mutant showed increased phosphorylation of SakA, the A. fumigatus Hog1 homologue. The schA null mutant has increased and decreased trehalose and glycerol accumulation, respectively, suggesting SchA performs different roles for glycerol and trehalose accumulation during osmotic stress. The schA was transcriptionally regulated by osmotic stress and this response was dependent on SakA and MpkC. The double ΔschA ΔsakA and ΔschA ΔmpkC mutants were more sensitive to osmotic stress than the corresponding parental strains. Transcriptomics and proteomics identified direct and indirect targets of SchA post‐exposure to hyperosmotic stress. Finally, ΔschA was avirulent in a low dose murine infection model. Our results suggest there is a complex network of interactions amongst the A. fumigatus TOR, SakA and SchA pathways.

    Item Type: Article
    Keywords: Aspergillus fumigatus SchASCH9 kinase; SakAHOG1 MAP kinase activity; virulence;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11157
    Identification Number: https://doi.org/10.1111/mmi.13484
    Depositing User: Dr. Sean Doyle
    Date Deposited: 08 Oct 2019 15:07
    Journal or Publication Title: Molecular Microbiology
    Publisher: John Wiley & Sons Ltd
    Refereed: Yes
    URI:

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