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The Aspergillus fumigatus SchA SCH9 kinase modulates SakA HOG1 MAP kinase activity and it is essential for virulence
Author(s) -
Alves de Castro Patrícia,
dos Reis Thaila Fernanda,
Dolan Stephen K.,
Oliveira Manfiolli Adriana,
Brown Neil Andrew,
Jones Gary W.,
Doyle Sean,
RiañoPachón Diego M.,
Squina Fábio Márcio,
Caldana Camila,
Singh Ashutosh,
Del Poeta Maurizio,
Hagiwara Daisuke,
SilvaRocha Rafael,
Goldman Gustavo H.
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13484
Subject(s) - biology , aspergillus fumigatus , protein kinase a , biochemistry , osmotic shock , kinase , mutant , microbiology and biotechnology , gene
Summary 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 Δ schA 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, Δ schA 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.